Expression profile of genes potentially associated with adequate glycemic control in patients with type 2 diabetes mellitus

CAPES - COORDENAÇÃO DE APERFEIÇOAMENTO DE PESSOAL DE NÍVEL SUPERIORFAPESP - FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULODespite increasing research in type 2 diabetes mellitus (T2D), there are few studies showing the impact of the poor glycemic control on biological processes occurring in T2D. In order to identify potential genes related to poorly/well-controlled patients2017CAPES - COORDENAÇÃO DE APERFEIÇOAMENTO DE PESSOAL DE NÍVEL SUPERIORFAPESP - FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULOCAPES - COORDENAÇÃO DE APERFEIÇOAMENTO DE PESSOAL DE NÍVEL SUPERIORFAPESP - FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULOsem informação2007/08362-82009/16233-92010/10882-

Evidence Linking PPARG Genetic Variants with Periodontitis and Type 2 Diabetes Mellitus in a Brazilian Population

The peroxisome proliferator-activated receptor gamma (PPARG) gene encodes a transcription factor involved in the regulation of complex metabolic and inflammatory diseases. We investigated whether single nucleotide polymorphisms (SNPs) and haplotypes of the PPARG gene could contribute with susceptibility to develop periodontitis alone or together with type 2 diabetes mellitus (T2DM). Moreover, we evaluated the gene–phenotype association by assessing the subjects’ biochemical and periodontal parameters, and the expression of PPARG and other immune response–related genes. We examined 345 subjects with a healthy periodontium and without T2DM, 349 subjects with moderate or severe periodontitis but without T2DM, and 202 subjects with moderate or severe periodontitis and T2DM. PPARG SNPs rs12495364, rs1801282, rs1373640, and rs1151999 were investigated. Multiple logistic regressions adjusted for age, sex, and smoking status showed that individuals carrying rs1151999-GG had a 64% lower chance of developing periodontitis together with T2DM. The CCGT haplotype increased the risk of developing periodontitis together with T2DM. The rs1151999-GG and rs12495364-TC were associated with reduced risk of obesity, periodontitis, elevated triglycerides, and elevated glycated hemoglobin, but there was no association with gene expression. Polymorphisms of the PPARG gene were associated with developing periodontitis together with T2DM, and with obesity, lipid, glycemic, and periodontal characteristics

Validation in a Brazilian population of gene markers of periodontitis previously investigated by GWAS and bioinformatic studies

Background: Bioinformatic tools and genome-wide association studies (GWAS) have led to comprehensive identification of single nucleotide polymorphisms (SNPs) associated with periodontitis in diverse populations. Here we aimed to detect and validate the association of seven SNPs as genetic markers of susceptibility to periodontitis in a Brazilian population. Methods: This case-control study assessed complete periodontal parameters of 714 subjects with periodontal status classified as healthy/mild periodontitis (n = 356) and moderate/severe periodontitis (n = 358). Genotyping for rs187238, rs352140, rs1360573, rs2521634, rs3811046, rs3826782, and rs7762544 SNPs were evaluated. Genetic-phenotype associations, and sex or smoking effects of SNPs on periodontitis were tested using multiple logistic regressions adjusted for covariates. Results: The rs2521634-AA (close to NPY gene) presented increased risk for severe periodontitis (OR = 2.34; 95% CI = 1.19–4.59). The rs3811046-GG (IL37 gene) demonstrated increased risk for moderate periodontitis (OR = 2.58; 95% CI = 1.28–5.18). Higher risk for moderate periodontitis was found in male with rs7762544-AG close to NCR2 gene. The rs352140-TT in the TLR9 gene proved to be associated with lower risk to severe periodontitis in men. The rs2521634-AA was associated with higher percentage of interproximal probing pocket depth (P =.004). Conclusions: This is the first evidence of validation in a Brazilian population of genetic markers of periodontitis previously investigated by GWAS and bioinformatics studies. SNPs in the NPY, IL37, and NCR2 genes were associated with susceptibility to moderate or severe periodontitis; whereas the TLR9 marker was associated with lower chance to develop severe periodontitis. Those SNPs had sex- and smoking-habit-specific effects on periodontitis; reinforcing the genetic profile predisposing to periodontitis

Frequencies Of The -330 (t → G) Il-2 And -590 (t → C) Il-4 Gene Polymorphisms In A Population From South-eastern Brazil

Polymorphisms in the promoter regions of cytokine genes may affect their transcription. A T/G substitution at position?330 of the interleukin-2 (IL-2) gene and a T/C substitution at position -590 of the interleukin-4 (IL-4) gene have been described previously. The -590 (T → C) IL-4 gene polymorphism was associated with asthma and atopy in US and Japanese populations. Population genetics is a useful tool for determination of the biological significance of genetic polymorphisms. The aim of this study was to investigate the frequencies of polymorphisms in the promoter regions of the IL-2 and IL-4 genes in a population from south-eastern Brazil and to compare them with those published for other populations. Allele frequencies were estimated in 114 unrelated individuals from São Paulo State. These subjects had an average age of 41.2 years (± 12.4 years) and the ethnic composition of the sample was: 78.07% Caucasian, 11.4% Black and 10.53% Mulatto. DNA from subjects was extracted from epithelial buccal cells, and the PCR-RFLP technique was employed to investigate the -330 (T → G) IL-2 and -590 (T → C) IL-4 gene polymorphisms. The allele frequency of the IL-2 gene polymorphism obtained in our study was similar to that found in UK Caucasoid groups. The T allele frequency of the IL-4 gene polymorphism observed in the Caucasian Brazilian group was similar to that found in UK and Australian populations, while the frequency observed for the Black Brazilian group was similar to that found in Japanese and Kuwaiti Arab populations. The results for the -330 (T → G) IL-2 and -590 (T → C) IL-4 polymorphisms are consistent with the high contribution of European lineages to the population in south-eastern Brazil.294293296Alves-Silva, J., Da Silva Santos, M., Guimaraes, P.E.M., Ferreira, A.C.S., Bandelt, H.-J., Pena, S.D.J., Prado, V.P., The ancestry of Brazilian mtDNA lineages (2000) American Journal of Human Genetics, 67, p. 444Arpini-Sampaio, Z., Costa, M.C.B., Melo, A.A., Carvalho, M.F.V.A., Deus, M.S.M., Simões, A.L., Genetic polymorphisms and ethnic admixture in African-derived Black communities of Notheastern Brazil (1999) Human Biology, 71, p. 69Callegari-Jacques, S.M., Salzano, F.M., Brazilian Indian/non-Indian interactions and their effects (1999) Ciência e Cultura, 51, p. 166Carvalho-Silva, D.R., Santos, F.R., Rocha, J., Pena, S.D., The phylogeography of Brazilian Y-chromosome lineages (2001) American Journal of Human Genetics, 68, p. 281Chen, Y.S., Torroni, A., Excoffier, L., Santachiara-Benerecetti, A.S., Wallace, D.C., Analysis of mtDNA variation in African populations reveals the most ancient of all human continent-specific haplogroups (1995) American Journal of Human Genetics, 57, p. 133Constans, J., DNA and protein polymorphism: Application to anthropology and human genetics (1988) Anthropologischer Anzeiger, 46, p. 97Faucz, F.R., Probst, C.M., Petzl-Erler, M.L., Polymorphism of LMP2 and TAP1, LMP7 and TAP2 in Brazilian Amerindians and Caucasoids: Implications for the evolution of allelic and haplotypic diversity (2000) European Journal of Immunogenetics, 27, p. 5Hijazi, Z., Haider, M.Z., Interleukin-4 gene promoter polymorphism [C590T] and asthma in Kuwaiti Arabs (2000) International Archives of Allergy and Immunology, 122, p. 190(2000) Brasil: 500 anos de Povoamento, , IBGE, Rio de JaneiroJohn, S., Turner, D., Donn, R., Sinnot, P., Worthington, J., Ollier, W.E.R., Hutchinson, I.V., Hajeer, A.H., Two novel biallelic polymorphism in the IL-2 gene (1998) European Journal of Immunogenetics, 25, p. 419Kornman, K.S., Crane, A., Wang, H.-Y., Di Giovine, F.S., Newman, M.G., Pirk, F.W., Wilson T.G., Jr., Duff, G.W., The interleukin-1 genotype as a severity factor in adult periodontal disease (1997) Journal of Clinical Periodontology, 24, p. 72Lazarus, M., Hajeer, A.H., Turner, D., Sinnott, P., Worthington, J., Ollier, W.E.R., Hutchinson, I.V., Genetic variation in the interleukin-10 gene promoter and systemic lupus erythematosus (1997) Journal of Rheumatology, 24, p. 2314Noguchi, E., Shibasaki, M., Arinami, T., Takeda, K., Yokouchi, Y., Kawashima, T., Yanagi, H., Hamaguchi, H., Association of asthma and the interleukin-4 promoter gene in Japanese (1998) Clinical and Experimental Allergy, 28, p. 449Probst, C.M., Bompeixe, E.P., Pereira, N.F., De Dalalio, M.M.O., Visentainer, J.E.I., Tsuneto, L.T., Petzl-Erler, M.L., HLA polymorphism and evaluation of European, African and Am erindian contribution to the white and mulatto populations from Paraná, Brazil (2000) Human Biology, 72, p. 597Reynard, M.P., Turner, D., Navarrete, C.V., Allele frequencies of polymorphisms of the tumor necrosis factor-α, interleukin-10, interferon-γ and interleukin-2 genes in a North European Caucasoid group from the UK (2000) European Journal of Immunogenetics, 27, p. 241Rosenwasser, L.J., Klemm, D.J., Dresback, J.K., Promoter polymorphisms in the chromosome 5 gene cluster in asthma and atopy (1995) Clinical and Experimental Allergy, 25 (SUPPL. 2), p. 74Scarel, R.M., Trevilatto, P.C., Di Hipólito O., Jr., Camargo, L.E.A., Line, S.R.P., Absence of mutations in the homeodomain of the MSX1 gene in patients with hypodontia (2000) American Journal of Medical Genetics, 92, p. 346Scarel-Caminaga, R.M., Trevilatto, P.C., Souza, A.P., Brito R.B., Jr., Line, S.R.P., Investigation of an IL-2 polymorphism in patients with different levels of chronic periodontitis (2002) Journal of Clinical Periodontology, , in pressSoares, J.F., Siqueira, A.L., (1999) Introdução á Estatística Médica, , Departamento de Estatística, Universidade Federal de Minas Gerais, Belo Horizonte, BrazilTrevilatto, P.C., Line, S.R.P., Use of buccal epithelial cells for PCR amplification of large DNA fragments (2000) Journal of Forensic Odonto-Stomatology, 31, p. 393Walley, A.J., Cookson, W.O.C.M., Investigation of an interleukin-4 promoter polymorphism for associations with asthma and atopy (1996) Journal of Medical Genetics, 33, p. 689Woolf, B., On estimating the relation between blood groups and disease (1955) Annals of Human Genetics, 19, p. 25

Evaluation Of The Relationship Between Interleukin-i Gene Cluster Polymorphisms And Early Implant Failure In Non-smoking Patients

Objective: The aim of the present study was to investigate the relationship between specific polymorphisms of the interleukin-1 gene cluster and the early failure of osseointegrated implants. Material and methods: The subject population was composed by a test group comprising 28 non-smoking patients (mean age 52.7) that had suffered one or more early implant failures and by a control group consisting of 34 individuals (mean age 43.3) with one or more healthy implants. Genomic DNA from buccal mucosa was amplified by the polymerase chain reaction (PCR), followed by restriction fragment length polymorphism (RFLP) and submitted to polyacrylamide gel electrophoresis to distinguish the alleles of the interleukin-1A (-889), interleukin-1B (+3953), interleukin-1B (-511) and interleukin-RN (intron 2) gene polymorphisms. Differences in the allele and genotype frequencies between control and test groups were assessed by χ2 test or by Monte Carlo simulations (P<0.05). Haplotype frequencies, linkage disequilibrium and Hardy-Weinberg equilibrium were also estimated. Results: No statistically significant differences were found in the genotype distribution or allelic frequencies of the polymorphisms. No differences were observed between control and test groups when different interleukin-1 gene cluster haplotypes were compared. Nevertheless, the interleukin-1A (-889) and interleukin-1B (+3953) polymorphic sites were in strong linkage disequilibrium (P = 0.00014 for control group and P = 0.0238 for the test group). Conclusion: This study suggests that polymorphisms in the interleukin-1 gene cluster are not associated with early implant failure in a non-smoking Brazilian population. Copyright © Blackwell Munksgaard 2004.162194201Adell, R., Eriksson, B., Lekholm, U., Branemark, P.I., Jemt, T., Long-term follow-up study of osseointegrated implants in the treatment of totally edentulous jaws (1990) International Journal of Oral & Maxillofacial Implants, 5, pp. 347-359Armitage, G.C., Wu, Y., Wang, H.Y., Sorrell, J., Di Giovine, F.S., Duff, G.W., Low prevalence of a periodontitis-associated interleukin-1 composite genotype in individuals of Chinese heritage (2000) Journal of Periodontology, 71, pp. 164-171Ayres, M., (1998) BioEstat: Statistical Applications in the Area of Medical and Biological Sciences (BioEstat: Aplicações Estatísticas Nas Áreas Das Ciências Biológicas e Médicas), , Manaus, Brazil: Sociedade Civil Mamirauá, MCT-CNPqBoiardi, L., Salvarani, C., Timms, J.M., Silvestri, T., Macchioni, P.L., Di Giovine, F.S., Interleukin-1 cluster and tumor necrosis factor-alpha gene polymorphisms in polymyalgia rheumatica (2000) Clinical and Experimental Rheumatology, 18, pp. 675-681Buchs, N., Di Giovine, F.S., Silvestri, T., Vannier, E., Duff, G.W., Miossec, P., IL-1B and IL-1Ra gene polymorphisms and disease severity in rheumatoid arthritis: Interaction with their plasma levels (2001) Genes and Immunity, 2, pp. 222-228Caffesse, R.G., De La Rosa, R.M., De La Rosa, G.M., Interleukin-1 gene polymorphism in a well-maintained periodontal patient population (2002) Brazilian Journal of Oral Sciences, 1, pp. 1-6Cork, M.J., Crane, A.M., Duff, G.W., Genetic control of cytokines. Cytokine gene polymorphisms in alopecia areata (1996) Dermatologic Clinics, 14, pp. 671-678Danis, V.A., Millington, M., Hyland, V.J., Grennan, D., Cytokine production by normal human monocytes: Inter-subject variation and relationship to an IL-1 receptor-antagonist (IL-1Ra) gene polymorphism (1995) Clinical and Experimental Immunology, 99, pp. 303-310Deas, D.E., Mikotowicz, J.J., Mackey, S.A., Moritz, A.J., Implant failure with spontaneous rapid exfoliation: Case reports (2002) Implant Dentistry, 11, pp. 235-242Di Giovine, F.S., Takhsh, E., Blackmore, A.L., Duff, G.W., Single base polymorphism at - 511 in the human interleukin-1β gene (IL-1β) (1992) Human Molecular Genetics, 1, p. 450Diehl, S.R., Wang, Y., Brooks, C.N., Burmeister, J.A., Califano, J.V., Wang, S., Schenkein, H.A., Linkage disequilibrium of interleukin-1 genetic polymorphisms with early-onset periodontitis (1999) Journal of Periodontology, 70, pp. 418-430Dinarello, C.A., Interleukin-1 and interleukin-1 antagonism (1991) Blood, 77, pp. 1627-1652Dinarello, C.A., Biologic basis for Interleukin-1 in disease (1996) Blood, 87, pp. 2095-2147Engebretson, S.P., Lamster, I.B., Herrera-Abreu, M., Celenti, R.S., Timms, J.M., Chaudhary, A.G., Di Giovine, F.S., Kornman, K.S., The influence of interleukin gene polymorphism on expression of interleukin-1beta and tumor necrosis factor-alpha in periodontal tissue and gingival crevicular fluid (1999) Journal of Periodontology, 70, pp. 567-573Esposito, M., Hirsch, J.M., Lekholm, U., Thomsen, P., Biological factors contributing to failures of osseointegrated oral implants. (I). Success criteria and epidemiology (1998) European Journal of Oral Sciences, 106, pp. 527-551Esposito, M., Hirsch, J.M., Lekholm, U., Thomsen, P., Biological factors contributing to failures of osseointegrated oral implants. (II). Etiopathogenesis (1998) European Journal of Oral Sciences, 106, pp. 721-764Feloutzis, A., Lang, N.P., Tonetti, M.S., Burgin, W., Bragger, U., Buser, D., Duff, G.W., Kornman, K.S., IL-1 gene polymorphism and smoking as risk factors for peri-implant bone loss in a wellmaintained population (2003) Clinical Oral Implants Research, 14, pp. 10-17Gemmell, E., Marshall, R.I., Seymour, G.J., Cytokines and prostaglandins in immune homeostasis and tissue destruction in periodontal disease (1997) Periodontology 2000, 14, pp. 112-143Genco, R.J., Host responses in periodontal diseases: Current concepts (1992) Journal of Periodontology, 63, pp. 338-355Gore, E.A., Sanders, J.J., Pandey, J.P., Palesch, Y., Galbraith, G.M., Interleukin-1beta + 3953 allele 2: Association with disease status in adult periodontitis (1998) Journal of Clinical Penodontology, 25, pp. 781-785Greenstein, G., Hart, T.C., A critical assessment of interleukin-1 (IL-1) genotyping when used in a genetic susceptibility test for severe chronic periodontitis (2002) Journal of Periodontology, 73, pp. 231-247Heresbach, D., Alizadeh, M., Dabadie, A., Le Berre, N., Colombel, J.F., Yaouanq, J., Bretagne, J.F., Semana, G., Significance of interleukin-1 beta and interleukin-1 receptor antagonist genetic polymorphism in inflammatory bowel diseases (1997) American Journal of Gastroenterology, 92, pp. 1164-1169Hurme, M., Santtila, S., IL-1 receptor antagonist (IL-1Ra) plasma levels are co-ordinately regulated by both IL-1Ra and IL-1beta genes (1998) European Journal of Immunology, 28, pp. 2598-2602Hutton, J.E., Heath, M.R., Chai, J.Y., Harnett, J., Jemt, T., Johns, R.B., McKenna, S., Taylor, R., Factors related to success and failure rates at 3-year follow-up in a multicenter study of overdentures supported by Branemark implants (1995) International Journal of Oral & Maxillofacial Implants, 10, pp. 33-42(2000) Brasil: 500 Anos de Povoamento, , Rio de Janeiro: IBGEKao, R.T., Curtis, D.A., Richards, D.W., Preble, J., Increased interleukin-1 beta in the crevicular fluid of diseased implants (1995) International Journal of Oral & Maxillofacial Implants, 10, pp. 696-701Karjalainen, J., Nieminen, M.M., Aromaa, A., Klaukka, T., Hurme, M., The IL-1beta genotype carries asthma susceptibility only in men (2002) The Journal of Allergy and Clinical Immunology, 109, pp. 514-516Kornman, K.S., Crane, A., Wang, H.Y., Di Giovine, F.S., Newman, M.G., Pirk, F.W., Wilson, T.G., Duff, G.W., The interleukin-1 genotype as a severity factor in adult periodontal disease (1997) Journal of Clinical Periodontology, 24, pp. 72-77Lekholm, U.G.J., Henry, P., Higuchi, K., Linden, U., Bergstrom, C., Van Steenberghe, D., Survival of the Branemark implant in partially edentulous jaws: A 0-10 year prospective multicenter study (1999) International Journal of Oral & Maxillofacial Implants, 14, pp. 636-645Lennard, A.C., Interleukin-1 receptor antagonist (1995) Critical Reviews in Immunology, 15, pp. 77-105Listgarten, M.A., Lang, N.P., Schroeder, H.E., Schroeder, A., Periodontal tissues and their counterparts around endosseous implants (1991) Clinical Oral Implants Research, 2, pp. 1-19Machado, J.C., Pharoah, P., Sousa, S., Carvalho, R., Oliveira, C., Figueiredo, C., Amorim, A., Sobrinho-Simoes, M., Interleukin 1B and interleukin 1RN polymorphisms are associated with increased risk of gastric carcinoma (2001) Gastroenterology, 121, pp. 823-829Maniatis, T., Fritsch, E.F., Sambrook, J., Construction of genomic libraries (1989) Molecular Cloning: A Laboratory Manual. 2nd Edition, , New York: Cold Spring Harbor Laboratory PressMansfield, J.C., Holden, H., Tarlow, J.K., Di Giovine, F.S., McDowell, T.L., Wilson, A.G., Holdsworth, C.D., Duff, G.W., Novel genetic association between ulcerative colitis and the anti-inflammatory cytokine interleukin-1 receptor antagonist (1994) Gastroenterology, 106, pp. 637-642McDevitt, M.J., Wang, H.Y., Knobelman, C., Newman, M.G., Di Giovine, F.S., Timms, J., Duff, G.W., Kornman, K.S., Interleukin-1 genetic association with periodontitis in clinical practice (2000) Journal of Periodontology, 71, pp. 156-163McDowell, T.L., Symons, J.A., Ploski, R., Fárre, O., Duff, G.W., A genetic association between juvenile rheumatoid arthritis and a novel interleukin-1 alpha polymorphism (1995) Arthritis and Rheumatism, 38, pp. 221-222Nemetz, A., Nosti-Escanilla, M.P., Molnar, T., Kope, A., Kovacs, A., Feher, J., Tulassay, Z., Pena, A.S., IL-1B gene polymorphisms influence the course and severity of inflammatory bowel disease (1999) Immunogenetics, 49, pp. 527-531Nguyen, L., Dewhirst, F.E., Hauschka, P.V., Stashenko, P., Interleukin-1 beta stimulates bone resorption and inhibits bone formation in vivo (1991) Lymphokine and Cytokine Research, 10, pp. 15-21Nicklin, M.J., Weith, A., Duff, G.W., A physical map of the region encompassing the human interleukin-1 alpha, interleukin-1 beta, and interleukin-1 receptor antagonist genes (1994) Genomics, 19, pp. 382-384Panagakos, F.S., Aboyoussef, H., Dondero, R., Jandinski, J.J., Detection and measurement of inflammatory cytokines in implant crevicular fluid: A pilot study (1996) International Journal of Oral & Maxillofacial Implants, 11, pp. 794-799Papapanou, P.N., Neiderud, A.M., Sandros, J., Dahlen, G., Interleukin-1 gene polymorphism and periodontal status. A case-control study (2001) Journal of Clinical Periodontology, 28, pp. 389-396Parfitt, A.M., The two faces of growth: Benefits and risks to bone integrity (1994) Osteoporosis International, 4, pp. 382-398Parkhill, J.M., Hennig, B.J., Chapple, I.L., Heasman, P.A., Taylor, J.J., Association of interleukin-1 gene polymorphisms with early-onset periodontitis (2000) Journal of Clinical Periodontology, 27, pp. 682-689Perala, D.G., Chapman, R.J., Gelfand, J.A., Complement activation by dental implants (1991) International Journal of Oral & Maxillofacial Implants, 6, pp. 136-141Perala, D.G., Chapman, R.J., Gelfand, J.A., Callahan, M.V., Adams, D.F., Lie, T., Relative production of IL-1 beta and TNF alpha by mononuclear cells after exposure to dental implants (1992) Journal of Periodontology, 63, pp. 426-430Pociot, F., Molvig, J., Wogensen, L., Worsaae, H., Nerup, J., A TaqI polymorphism in the human interleukin-1 beta (IL-1 beta) gene correlates with IL-1 beta secretion in vitro (1992) European Journal of Clinical Investigations, 22, pp. 396-402Read, R.C., Camp, N.J., Di Giovine, F.S., Borrow, R., Kaczmarski, E.B., Chaudhary, A.G., Fox, A.J., Duff, G.W., An interleukin-1 genotype is associated with fatal outcome of meningococcal disease (2000) The Journal of Infectious Diseases, 182, pp. 1557-1560Rogers, M.A., Figliomeni, L., Baluchova, K., Tan, A.E., Davies, G., Henry, P.J., Price, P., Do interleukin-1 polymorphisms predict the development of periodontitis or the success of dental implants? (2002) Journal of Periodontology, 37, pp. 37-41Salcetti, J.M., Moriarty, J.D., Cooper, L.F., Smith, F.W., Collins, J.G., Socransky, S.S., Offenbacher, S., The clinical, microbial, and host response characteristics of the failing implant (1997) International Journal of Oral & Maxillofacial Implants, 12, pp. 32-42Sanguinetti, C.J., Dias, E.N., Simpson, A.J.G., Rapid silver staining and recovery of PCR products separated on polyacrylamide gels (1994) Biotechniques, 17, pp. 915-919Santilla, S., Savinainen, K., Hurme, M., Presence of the IL-1RA allele 2 (IL-1RN*2) is associated with enhanced IL-1 beta production in vitro (1998) Scandinavian Journal of Immunology, 47, pp. 195-198Santos, M.C.L.G., Campos, M.I.G., Line, S.R.P., Early dental implant failure: A review of literature (2002) Brazilian Journal of Oral Sciences, 1, pp. 103-111Schneider, S., Roessli, D., Excoffier, E., (2000) ARLEQUIM Ver. 2000: A Software for Population Genetic Data Analysis, , University of Geneva, Switzerland: Genetics and Biometry LaboratorySchwartz, Z., Lohmann, C.H., Cochran, D.L., Sylvia, V.L., Dean, D.D., Boyan, B.D., Bone regulating mechanisms on implant surfaces (1999) Proceedings of the 3rd European Workshop on Periodontology: Implant Dentistry. 1st Edition, pp. 41-54. , Lang, N.P., Karring, T. & Lindhe, J., eds., Chicago: Quintessence PublishingSham, P.C., Curtis, D., Monte Carlo tests for associations between disease and alleles at highly polymorphic loci (1995) Annals of Human Genetics, 59, pp. 97-105Shirodaria, S., Smith, J., McKay, I.J., Kennet, C.N., Hugh, F.J., Polymorphisms in the IL-1A gene are correlated with levels of interleukin-1 alpha protein in gingival crevicular fluid of teeth with severe periodontal disease (2000) Journal of Dental Research, 79, pp. 1864-1869Stashenko, P., Dewhirst, F.E., Peros, W.J., Kent, R.L., Ago, J.M., Synergistic interactions between interleukin 1, tumor necrosis factor, and lymphotoxin in bone resorption (1987) Journal of Immunology, 138, pp. 1464-1468Takamatsu, M., Yamauchi, M., Maezawa, Y., Saito, S., Maeyama, S., Uchikoshi, T., Genetic polymorphisms of interleukin-1 beta in association with the development of alcoholic liver disease in Japanese patients (2000) American Journal of Gastroenterology, 95, pp. 1305-1311Tarlow, J.K., Blakemore, A.I.F., Lennard, A., Solari, R., Steinkasserer, A., Duff, G.W., Polymorphism in human IL-1 receptor antagonist gene intron 2 is caused by variable numbers of an 86-bp tandem repeat (1993) Human Genetics, 91, pp. 403-404Tatakis, D.N., Interleukin-1 and bone metabolism: A review (1993) Journal of Periodontology, 64, pp. 416-431Trevilatto, P.C., Line, S.R.P., Use of buccal epithelial cells for PCR amplification of large DNA fragments (2000) Journal of Forensic Odonto-Stomatology, 18, pp. 6-9Tsutsui, T., Kawaguchi, H., Fujino, A., Sakai, A., Kaji, H., Nakamura, T., Exposure of macrophage-like cells to titanium particles does not affect bone resorption, but inhibits bone formation (1999) Journal of Orthopedic Science, 4, pp. 32-38Walker, S.J., Van Dyke, T.E., Rich, S., Kornman, K.S., Di Giovine, F.S., Hart, T.C., Genetic polymorphisms of the IL-1alpha and IL-1beta genes in African-American LJP patients and an African-American control population (2000) Journal of Periodontology, 71, pp. 723-728Weyant, R.J., Burt, B.A., An assessment of survival rates and within-patient clustering of failures for endosseous oral implants (1993) Journal of Dental Research, 72, pp. 2-8Wilson Jr., T.G., Nunn, M., The relationship between the interleukin-1 periodontal genotype and implant loss. Initial Data (1999) Journal of Periodontology, 70, pp. 724-72

Early Failure Of Dental Implants And Tnf-α (g-308a) Gene Polymorphism

Tumor necrosis factor-α (TNF-α) is a potent inflammatory mediator with bone resorption activity. Polymorphisms in the promoter region of the human TNF-α gene have been shown to affect the levels of this cytokine and have been associated with a variety of diseases. The aim of this study was to investigate the possible relationship between early implant failure and a single nucleotide polymorphism (SNP) in the -308 promoter region of the TNF-α gene. A sample of 66 nonsmokers was divided into 2 groups: a test group comprising 28 patients (mean age, 52.7 years) with one or more early failed implants and a control group consisting of 38 individuals (mean age, 43.2 years) with one or more healthy implants. Genomic DNA from buccal mucosa was amplified by the polymerase chain reaction (PCR), analyzed by restriction fragment length polymor phism (RFLP), and submitted to polyacrylamide gel electrophoresis to distinguish allele G and allele A of the TNF-α (-308) gene polymorphism. Differences in the allele and genotype frequencies between control and test groups were assessed by chi-squared test (P <0.05). No significant difference was observed in the allele (P = 0.4635) and genotype (P = 0.4445) distribution of the polymorphism when control and failure groups were compared. The results indicate that the TNF-α (G-308A) gene polymorphism is not associated with early implant failure, suggesting that its presence alone does not constitute a genetic risk factor for implant loss in the Brazilian population. Copyright © 2004 by Lippincott Williams & Wilkins.13195101Adell, R., Eriksson, B., Lekholm, U., Long-term follow-up study of osseointegrated implants in the treatment of totally edentulous jaws (1990) Int J Oral Maxillofac Implants, 5, pp. 347-359Lekholm, U.G.J., Henry, P., Higuchi, K., Survival of the Branemark implant in partially edentulous jaws: A 0-10 year prospective multicenter study (1999) Int J Oral Maxillofac Implants, 14, pp. 636-645Esposito, M., Hirsch, J.M., Lekholm, U., Biological factors contributing to failures of osseointegrated oral implants. (I). Success criteria and epidemiology (1998) Eur J Oral Sci, 106, pp. 527-551El Askary, A.S., Meffert, R.M., Griffin, T., Why do dental implants fail? Part I (1999) Implant Dentistry, 8, pp. 173-185Parfitt, A.M., The two faces of growth: Benefits and risks to bone integrity (1994) Osteoporos Int, 4, pp. 382-398Horowitz, M.C., Lorenzo, J.A., (1996) Local Regulators of Bone, 1st Ed., pp. 687-700. , New York: Academic PressBeutler, B., Cerami, A., The biology of cachectin/TNF - A primary mediator of the host response (1989) Annu Rev Immunol, 7, pp. 625-655Vassalli, P., The pathophysiology of tumor necrosis factors (1992) Annu Rev Immunol, 10, pp. 411-452Manogue, K.R., Van Deventer, S.J.H., Cerami, A., (1991) Tumor Necrosis Factor or Cachectin, 1st Ed., pp. 241-256. , New York: Academic PressMeikle, M.C., Atkinson, S.J., Ward, R.V., Gingival fibroblasts degrade type I collagen films when stimulated with tumor necrosis factor and interleukin 1: Evidence that breakdown is mediated by metalloproteinases (1989) J Periodontal Res, 24, pp. 207-213Elias, J.A., Gustilo, K., Baeder, W., Synergistic stimulation of fibroblast prostaglandin production by recombinant interleukin 1 and tumor necrosis factor (1987) J Immunol, 138, pp. 3812-3816Chaudhary, L.R., Spelsberg, T.C., Riggs, B.L., Production of various cytokines by normal human osteoblast-like cells in response to interleukin-1 beta and tumor necrosis factor-alpha: Lack of regulation by 17 beta-estradiol (1992) Endocrinology, 130, pp. 2528-2534Bertolini, D.R., Nedwin, G.E., Bringman, T.S., Stimulation of bone resorption and inhibition of bone formation in vitro by human tumor necrosis factors (1986) Nature, 319, pp. 516-518Van Der Pluijm, G., Most, W., Van Der Wee-Pals, L., Two distinct effects of recombinant human tumor necrosis factor-alpha on osteoclast development and subsequent resorption of mineralized matrix (1991) Endocrinology, 129, pp. 1596-1604Johnson, R.A., Boyce, B.F., Mundy, G.R., Tumors producing human tumor necrosis factor induced hypercalcemia and osteoclastic bone resorption in nude mice (1989) Endocrinology, 124, pp. 1424-1427Feldman, M., TNF-α: A pivotal role in rheumatoid arthritis (1992) Br J Rheumatol, 6, pp. 485-516Jacob, C.O., Fronek, Z., Lewis, G.D., Heritable major histocompatibility complex class Lis associated differences in production of tumor necrosis factor-α relevance to genetic predisposition to systemic lupus erythematosus (1990) Proc Natl Acad Sci U S A, 87, pp. 1233-1237Zinman, B., Hanley, A.J.G., Harris, S.B., Circulating tumor necrosis factor-α concentrations in a native Canadian population with high rates of type 2 diabetes mellitus (1999) J Clin Endocrinol Metab, 84, pp. 272-278Galbraith, G.M., Steed, R.B., Sanders, J.J., Tumor necrosis factor alpha production by oral leukocytes: Influence of tumor necrosis factor genotype (1998) J Periodontol, 69, pp. 428-433Stashenko, P., Jandinski, J.J., Fujiyoshi, P., Tissue levels of bone resorptive cytokines in periodontal disease (1991) J Periodontol, 62, pp. 504-509Rossomando, E.F., Kennedy, J.E., Hadjimichael, J., Tumor necrosis factor alpha in gingival crevicular fluid as a possible indicator of periodontal disease in humans (1990) Arch Oral Biol, 35, pp. 431-434Wilson, A.G., Di Giovine, F.S., Blakemore, A.I., Single base polymorphism in the human tumor necrosis factor alpha (TNF alpha) gene detectable by Ncol restriction of PCR product (1992) Hum Mol Genet, 1, p. 353Kroeger, K.M., Carville, K.S., Abraham, L.J., The -308 tumor necrosis factor-alpha promoter polymorphism effects transcription (1997) Mol Immunol, 34, pp. 391-399Wilson, A.G., Symons, J.A., McDowell, T.L., Effects of a polymorphism in the human tumor necrosis factor alpha promoter on transcriptional activation (1997) Proc Natl Acad Sci U S A, 94, pp. 3195-3199Brinkman, B.M., Zuijdeest, D., Kaijzel, E.L., Relevance of the tumor necrosis factor alpha (TNF alpha) -308 promoter polymorphism in TNF alpha gene regulation (1995) J Inflamm, 96 (46), pp. 32-41Perry, R.T., Collins, J.S., Wiener, H., The role of TNF and its receptors in Alzheimer's disease (2001) Neurobiol Aging, 22, pp. 873-883Danis, V.A., Millington, M., Hyland, V., Increased frequency of the uncommon allele of a tumor necrosis factor alpha polymorphism in rheumatoid arthritis and systemic lupus erythematosus (1995) Dis Markers, 12, pp. 127-133Rood, M.J., Van Krugten, M.V., Zanelli, E., TNF -308 and HLA-DR3 alleles contribute independently to susceptibility to systemic lupus erythematosus (2000) Arthritis Rheum, 43, pp. 129-134Witte, J.S., Palmer, L.J., O'Connor, R.D., Relation between tumor necrosis factor polymorphism TNFalpha -308 and risk of asthma (2002) Eur J Hum Genet, 10, pp. 82-85Heijmans, B.T., Westendorp, R.G., Droog, S., Association of the tumor necrosis factor alpha -308G/A polymorphism with the risk of diabetes in an elderly population-based cohort (2002) Genes Immun, 3, pp. 225-228Kao, R.T., Curtis, D.A., Richards, D.W., Increased interleukin-1 beta in the crevicular fluid of diseased implants (1995) Int J Oral Maxillofac Implants, 10, pp. 696-701Panagakos, F.S., Aboyoussef, H., Dondero, R., Detection and measurement of inflammatory cytokines in implant crevicular fluid: A pilot study (1996) Int J Oral Maxillofac Implants, 11, pp. 794-799Salcetti, J.M., Moriarty, J.D., Cooper, L.F., The clinical, microbial, and host response characteristics of the failing implant (1997) Int J Oral Maxillofac Implants, 12, pp. 32-42Schwartz, Z., Lohmann, C.H., Cochran, D.L., (1999) Bone Regulating Mechanisms on Implant Surfaces, 1st Ed., pp. 41-54. , Chicago: Quintessence PublishingVan Der Linden, M.W., Huizinga, T.W., Stoeken, D.J., Determination of tumor necrosis factor-alpha and interleukin-10 production in a whole blood stimulation system: Assessment of laboratory error and individual variation (1998) J Immunol Methods, 218, pp. 63-71Westendorp, R.G., Langermans, J.A., Huizinga, T.W., A genetic influence on cytokine production in meningococcal disease (1997) Lancet, 349, pp. 1912-1913Trevilatto, P.C., Line, S.R.P., Use of buccal epithelial cells for PCR amplification of large DNA fragments (2000) J Forensic Odontostomatol, 18, pp. 6-9Maniatis, T., Fritsch, E.F., Sambrook, J., (1989) Molecular Cloning: A Laboratory Manual, 2nd Ed., pp. 458-463. , New York: Cold Spring Harbor Laboratory PressSanguinetti, C.J., Dias, E.M., Simpson, A.J.G., Rapid silver staining and recovery of PCR products separated on polyacrylamide gels (1994) Biotechniques, 17, pp. 915-919Esposito, M., Hirsch, J.M., Lekholm, U., Biological factors contributing to failures of osseointegrated oral implants. (II). Etiopathogenesis (1998) Eur J Oral Sci, 106, pp. 721-764Santos, M.C.L.G., Campos, M.I.G., Line, S.R.P., Early dental implant failure: A review of literature (2002) Braz J Oral Sci, 1, pp. 103-111El Askary, A.S., Meffert, R.M., Griffin, T., Why do dental implants fail? Part II (1999) Implant Dentistry, 8, pp. 265-277Deas, D.E., Mikotowicz, J.J., Mackey, S.A., Implant failure with spontaneous rapid exfoliation: Case reports (2002) Implant Dentistry, 11, pp. 235-242Weyant, R.J., Burt, B.A., An assessment of survival rates and within-patient clustering of failures for endosseous oral implants (1993) J Dent Res, 72, pp. 2-8Hutton, J.E., Heath, M.R., Chai, J.Y., Factors related to success and failure rates at 3-year follow-up in a multicenter study of overdentures supported by Branemark implants (1995) Int J Oral Maxillofac Implants, 10, pp. 33-42Deem, L.P., Bassiouny, M.A., Deem, T.E., The sequential failure of osseointegrated submerged implants (2002) Implant Dentistry, 11, pp. 243-248Ekfeldt, A., Christiansson, U., Eriksson, T., A retrospective analysis of factors associated with multiple implant failures in maxillae (2001) Clin Oral Implants Res, 12, pp. 462-467Wilson, T.G.J., Nunn, M., The relationship between the interleukin-1 periodontal genotype and implant loss. Initial data (1999) J Periodontol, 70, pp. 724-729Kornman, K.S., Crane, A., Wang, H.Y., The interleukin-1 genotype as a severity factor in adult periodontal disease (1997) J Clin Periodontol, 24, pp. 72-77Rogers, M.A., Figliomeni, L., Baluchova, K., Do interleukin-1 polymorphisms predict the development of periodontitis or the success of dental implants? (2002) J Periodontol, 37, pp. 37-41Feloutzis, A., Lang, N.P., Tonetti, M.S., IL-1 gene polymorphism and smoking as risk factors for peri-implant bone loss in a well-maintained population (2003) Clin Oral Implants Res, 14, pp. 10-17Wilson, A.G., Vries, N., Pociot, F., An allelic polymorphism within the human tumor necrosis factor α promoter region is strongly associated with HLA A1, B8, and DR3 alleles (1993) J Exp Med, 117, pp. 557-560Abraham, L.J., French, M.A.H., Dawkins, R.L., Polymorphic MHC ancestral haplotypes affect the activity of tumor necrosis factor-alpha (1993) Clin Exp Immunol, 92, pp. 14-18Perrey, C., Pravica, V., Sinnott, P.J., Genotyping for polymorphisms in interferon-gamma, interleukin-10, transforming growth factor-beta 1 and tumour necrosis factor-alpha genes: A technical report (1998) Transpl Immunol, 6, pp. 193-197Perala, D.G., Chapman, R.J., Gelfand, J.A., Relative production of IL-1 beta and TNF alpha by mononuclear cells after exposure to dental implants (1992) J Periodontol, 63, pp. 426-430Tsutsui, T., Kawaguchi, H., Fujino, A., Exposure of macrophage-like cells to titanium particles does not affect bone resorption, but inhibits bone formation (1999) J Orthop Sci, 4, pp. 32-3

Interleukin-2 And Interleukin-6 Gene Promoter Polymorphisms, And Early Failure Of Dental Implants

Single nucleotide polymorphisms in the promoter region of the human interleukin (IL)-2 (T-330G) and IL-6 (G-174C) genes have modified the transcriptional activity of these cytokines and are associated with several diseases. The aim of this study was to investigate the possible relationship between these single nucleotide polymorphisms and early implant failure. A sample of 74 nonsmokers was divided into 2 groups: test group comprising 34 patients (mean age 49.3 years) with ĝ‰¥1 implants that failed and control group consisting of 40 patients (mean age 43.8 years) with ĝ‰¥1 healthy implants. Genomic deoxyribonucleic acid from oral mucosa was amplified by polymerase chain reaction and analyzed by restriction fragment length polymorphism. Monte Carlo simulations (P G) IL-2 and -590 (T -> C) IL-4 gene polymorphisms in a population from south-eastern Brazil (2002) Eur J Immunogenet., 29, pp. 293-296Reynard, M.P., Turner, D., Navarrete, C.V., Allele frequencies of polymorphisms of the tumour necrosis factor-alpha, interleukin-10, interferon-gamma and interleukin-2 genes in a North European Caucasoid group from the UK (2000) Eur J Immunogenet., 27, pp. 241-249Perala, D.G., Chapman, R.J., Gelfand, J.A., Relative production of IL-1 beta and TNF alpha by mononuclear cells after exposure to dental implants (1992) J Periodontol., 63, pp. 426-430Wang, J.Y., Tsukayama, D.T., Wicklund, B.H., Inhibition of T and B cell proliferation by titanium, cobalt, and chromium: Role of IL-2 and IL-6 (1996) J Biomed Mater Res., 32, pp. 655-661Nakashima, Y., Sun, D.H., Trindade, M.C., Signaling pathways for tumor necrosis factor-alpha and interleukin-6 expression in human macrophages exposed to titanium-alloy particulate debris in vitro (1999) J Bone Joint Surg., 81, pp. 603-615Shida, J., Trindade, M.C., Goodman, S.B., Induction of interleukin-6 release in human osteoblast-like cells exposed to titanium particles in vitro (2000) Calcif Tissue Int., 67, pp. 151-155Horowitz, S.M., Gonzales, J.B., Inflammatory response to implant particulates in a macrophage/osteoblast coculture model (1996) Calcif Tissue Int., 59, pp. 392-39