Interleukin-8-251T > A, Interleukin-1α-889C > T and Apolipoprotein E polymorphisms in Alzheimer's disease.

An inflammatory process has been involved in numerous neurodegenerative disorders such as Parkinson's disease, stroke and Alzheimer's disease (AD). In AD, the inflammatory response is mainly located in the vicinity of amyloid plaques. Cytokines, such as interleukin-8 (IL-8) and interleukin-1α (IL-1α), have been clearly involved in this inflammatory process. Polymorphisms of several interleukin genes have been correlated to the risk of developing AD. The present study investigated the association of AD with polymorphisms IL-8 -251T > A (rs4073) and IL-1α-889C > T (rs1800587) and the interactive effect of both, adjusted by the Apolipoprotein E genotype. 199 blood samples from patients with AD, 146 healthy elderly controls and 95 healthy young controls were obtained. DNA samples were isolated from blood cells, and the PCR-RFLP method was used for genotyping. The genotype distributions of polymorphisms IL-8, IL-1α and APOE were as expected under Hardy-Weinberg equilibrium. The allele frequencies did not differ significantly among the three groups tested. As expected, the APOE4 allele was strongly associated with AD (p A and IL-1α-889C > T were not found to be risk factors for AD

Exposição a pesticidas e genótipo heterozigoto de GSTP1-Alw26I associam-se à doença de Parkinson

Objective This study aimed to analyze the frequency of GSTP1-Alw26I polymorphism and to estimate its association with toxic substances in Parkinson's disease (PD). Methods A study group with 154 patients - subdivided into familial and sporadic PD groups - and 158 elderly individuals without the disease (control group) were evaluated. GSTP1-Alw26I polymorphism was analyzed by polymerase chain reaction/restriction fragment length polymorphism (PCR-RFLP). Results Patients were significantly more exposed to pesticides compared with the control group (p=0.0004), and the heterozygote genotype associated to exposure to pesticides also prevailed in patients (p=0.0001). Wild homozygote genotype was related to tobacco use (p=0.043) and alcoholism (p=0.033) in familial PD patients. Conclusion Exposure to pesticides is associated to PD, whose effect can be enhanced when combined with the heterozygote genotype of GSTP1-Alw26I. Also, large genetic and environmental studies considering tobacco use, alcoholism, GSTP1 and PD are necessary to confirm our findings.Objetivo Analisar a frequência do polimorfismo GSTP1-Alw26I, assim como estimar sua associação com substâncias tóxicas na doença de Parkinson (DP). Métodos A casuística avaliada foi composta por um grupo de estudo, com 154 pacientes, subdivididos em DP familial e esporádica, e outro com 158 idosos sem a doença (grupo controle). O polimorfismo GSTP1-Alw26I foi analisado por reação em cadeia da polimerase/polimorfismo de comprimento do fragmento de restrição (PCR/RFLP). Resultados Os pacientes foram significativamente mais expostos a pesticidas, comparados com o grupo controle (p=0,0004), e o genótipo heterozigoto associado a exposição a pesticidas também prevaleceu nos pacientes (p=0,0001). O genótipo homozigoto selvagem apresentou relação com tabagismo (p=0,043) e etilismo (p=0,033) em pacientes com DP familial. Desse modo, a exposição a pesticidas está associada à DP, cujo efeito pode ser potencializado quando combinado ao genótipo heterozigoto de GSTP1-Alw26I. Estudos genético-ambientais envolvendo tabagismo, etilismo, GSTP1 e DP devem ser realizados em casuísticas numerosas, confirmando essa associação.Sao Jose do Rio Preto Medical School Department of NeuroscienceFAMERPFederal University of São PauloHospital de BaseUNIFESPSciEL

Association of interleukin 1 beta polymorphisms and haplotypes with Alzheimer's disease

Our study aimed to associate IL-1 beta and IL-1RN polyrnorphisms with AD disease in comparison with elderly control group from São Paulo - Brazil. We genotyped 199 Alzheimer's disease (AD) patients, 165 elderly control and 122 young control samples, concerning VNTR (IL-1RN) and -511C>T and -31T>C (IL-1 beta) polymorphisms. Our findings revealed that -511C/-31T/2-repetitions VNTR haplotype had a protective effect for AD when compared to EC (p=0.005), whereas -511C/-31C/1-repetition VNTR haplotype was associated as a risk factor for AD (p=0.021). Taken together, we may suggest that there is a relevant role of IL-1 genes cluster in AD pathogenesis in this Brazilian population. (c) 2012 Elsevier B.V. All rights reserved.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Universidade do Sagrado Coracao de BauruConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Faculdade de Medicina de Marilia (FAMEMA)USC, São Paulo, BrazilUniversidade Federal de São Paulo, Escola Paulista Med UNIFESP EPM, Dept Morfol, Disciplina Genet, São Paulo, BrazilUniversidade Federal de São Paulo, Escola Paulista Med UNIFESP EPM, Disciplina Neurol Ambulatorio Neurol Comportament, São Paulo, BrazilFac Med Marilia FAMEMA, Hemoctr, Disciplina Genet, São Paulo, BrazilFac Med Sao Jose do Rio Preto, Nucleo Pesquisa Bioquim & Biol Mol, São Paulo, BrazilUniv Marilia UNIMAR, Fac Med, São Paulo, BrazilUniversidade Federal de São Paulo, Escola Paulista Med UNIFESP EPM, Dept Morfol, Disciplina Genet, São Paulo, BrazilUniversidade Federal de São Paulo, Escola Paulista Med UNIFESP EPM, Disciplina Neurol Ambulatorio Neurol Comportament, São Paulo, BrazilFAPESP: 06/07240-3FAPESP: 09/15857-9FAPESP: 04/15273-3Web of Scienc

Nulidade de GSTT1/GSTM1 relacionada a pesticidas associa-se com doenca de Parkinson

Genetic and environmental factors affect the pathogenesis of Parkinson's disease(PD). Genetic variants of the enzyme glutathione S-transferases (GST) may be relatedto the disease. This study aimed to evaluate the influence of genetic variants of GST(GSTT1/GSTM1) and their association with the exposure to environmental toxins in PDpatients. We studied 254 patients with PD and 169 controls. The GSTM1/GSTT1 variantwere analyzed by polymerase chain reaction. We applied the Fisher's exact test andthe χ2 test for statistical analysis (p<0.05). The present andabsence for GSTT1 and GSTM1 were similar in patients and controls. The null for GSTT1and GSTM1 (0/0) and exposure to pesticides prevailed in patients (18%) compared tocontrols (13%, p=0.014). This study suggests the association between PD and previouexposure to pesticides, whose effect may be enhanced in combination with null forGSTT1/GSTM1.Fatores genéticos e ambientais influenciam a patogênese da doença de Parkinson (DP).Variantes genéticas das enzimas glutationa S-transferases (GST) parecem estarenvolvidas com a doença. Os objetivos deste estudo foram avaliar a influência devariantes genéticas de GST (GSTT1/GSTM1) e sua associação com exposição a toxinaambientais em pacientes com DP. Foram estudados 254 pacientes com DP e 169 controles.As variantes para GSTM1/GSTT1 foram analisadas por reação em cadeia da polimerase.Para análise estatística foram aplicados os testes de Fisher e do χ2(p<0,05). Tanto a presença quanto a nulidade para GSTT1 e GSTM1 foramsemelhantes em pacientes e controles. A nulidade para GSTT1 e GSTM1 (0/0) e contatocom agrotóxicos prevaleceu nos pacientes (18%) em relação aos controles (13%,p=0,014). Este estudo sugere associação entre DP e contato prévio com agrotóxicos,cujo efeito parece potencializado em combinação com nulidade para GSTT1/GSTM1.FAMERPUniversidade Federal de São Paulo (UNIFESP)FAMERP Department of NeuroscienceFAMERP Hospital de BaseUNIFESPSciEL

Novel Zinc-Related Differentially Methylated Regions in Leukocytes of Women With and Without Obesity

INTRODUCTION: Nutriepigenetic markers are predictive responses associated with changes in “surrounding” environmental conditions of humans, which may influence metabolic diseases. Although rich in calories, Western diets could be linked with the deficiency of micronutrients, resulting in the downstream of epigenetic and metabolic effects and consequently in obesity. Zinc (Zn) is an essential nutrient associated with distinct biological roles in human health. Despite the importance of Zn in metabolic processes, little is known about the relationship between Zn and epigenetic. Thus, the present study aimed to identify the epigenetic variables associated with Zn daily ingestion (ZnDI) and serum Zinc (ZnS) levels in women with and without obesity. MATERIALS AND METHODS: This is a case-control, non-randomized, single-center study conducted with 21 women allocated into two groups: control group (CG), composed of 11 women without obesity, and study group (SG), composed of 10 women with obesity. Anthropometric measurements, ZnDI, and ZnS levels were evaluated. Also, leukocyte DNA was extracted for DNA methylation analysis using 450 k Illumina BeadChips. The epigenetic clock was calculated by Horvath method. The chip analysis methylation pipeline (ChAMP) package selected the differentially methylated regions (DMRs). RESULTS: The SG had lower ZnS levels than the CG. Moreover, in SG, the ZnS levels were negatively associated with the epigenetic age acceleration. The DMR analysis revealed 37 DMRs associated with ZnDI and ZnS levels. The DMR of PM20D1 gene was commonly associated with ZnDI and ZnS levels and was hypomethylated in the SG. CONCLUSION: Our findings provide new information on Zn's modulation of DNA methylation patterns and bring new perspectives for understanding the nutriepigenetic mechanisms in obesity

14-weeks combined exercise epigenetically modulated 118 genes of menopausal women with prediabetes

Background: Pre-diabetes precedes Diabetes Mellitus (DM) disease and is a critical period for hyperglycemia treatment, especially for menopausal women, considering all metabolic alterations due to hormonal changes. Recently, the literature has demonstrated the role of physical exercise in epigenetic reprogramming to modulate the gene expression patterns of metabolic conditions, such as hyperglycemia, and prevent DM development. In the present study, we hypothesized that physical exercise training could modify the epigenetic patterns of women with poor glycemic control. Methods: 48 post-menopause women aged 60.3 ± 4.5 years were divided according to their fasting blood glucose levels into two groups: Prediabetes Group, PG (n=24), and Normal Glucose Group, NGG (n=24). All participants performed 14 weeks of physical exercise three times a week. The Infinium Methylation EPIC BeadChip measured the participants’ Different Methylated Regions (DMRs). Results: Before the intervention, the PG group had 12 DMRs compared to NGG. After the intervention, five DMRs remained different. Interestingly, when comparing the PG group before and after training, 118 DMRs were found. The enrichment analysis revealed that the genes were related to different biological functions such as energy metabolism, cell differentiation, and tumor suppression. Conclusion: Physical exercise is a relevant alternative in treating hyperglycemia and preventing DM in post-menopause women with poor glycemic control

Polimorfismo da apolipoproteína e nos familiares em primeiro grau de pacientes com doença de Alzheimer familial ou esporádica Apolipoprotein e polymorphism in first-degree relatives of patients with familial or sporadic Alzheimer's disease

INTRODUÇÃO: A apolipoproteína E (apo E) é reconhecida como fator de risco para doença de Alzheimer (DA). OBJETIVO: Analisar o polimorfismo da apo E nos familiares em primeiro grau de pacientes com DA familial ou esporádica do tipo tardio, comparando a famílias sem DA. MÉTODO: Foram estudados 40 pacientes com DA familial ou esporádica do tipo tardio, sendo os grupos classificados como provável, segundo critérios da NINCS-ADRDA. RESULTADO: O alelo épsilon3 foi o mais freqüente em todos os grupos. Observou-se freqüência mais elevada de épsilon4 comparando os familiares dos probandos aos do grupo controle (p<0,0001). O alelo épsilon2 mostrou diferença significante apenas entre familiares do grupo controle e DA familial (p=0,026). CONCLUSÃO: O polimorfismo da apo E não diferencia DA familial da esporádica. O estudo de famílias permite amplificar a representatividade dos alelos épsilon2 e épsilon4, revelando, seu valor como fator protetor e de risco para DA, respectivamente.<br>INTRODUCTION: Apolipoproteín E (apo E) has been recognized as a risk factor for Alzheimer disease (AD). OBJECTIVE: To analyze apo E polymorphism in first-degree relatives of patients with familial or sporadic late-onset AD comparing with families without AD. METHOD: Forty patients with familial or sporadic late-onset of AD, being both groups classified as probable, according of NINCS-ADRDA’s criteria. RESULTS: Allele epsilon3 was the most frequent in all of these groups. Higher frequency of epsilon4 when comparing the relatives of the probands with the relatives of the control group (p<0,0001) was observed. Allele epsilon2 showed significant difference only between relatives of familial AD and relatives of control group (p=0,026). CONCLUSION: Apo E polymorphism has not differentiated familial from sporadic AD. The study of families allows to amplify the alelles epsilon2 and epsilon4 representativity, revealing, their value as protecting factor and of risk for AD, respectively