Interleukin-10G and interleukin-10R microsatellite polymorphisms and osteoarthritis of the knee

Objective To clarify and evaluate the possible role of interleukin-10G (IL-10G) and interleukin-10R (IL-10R) microsatellite polymorphisms of IL-10 gene in knee osteoarthritis (OA). Methods This was a case-control study. Our population consisted of 132 patients with primary knee osteoarthritis who had undergone total knee replacement (TKR) and 165 unaffected controls. Peripheral blood was used to extract genomic DNA and the IL-10G and IL-10R polymorphisms were examined by a polymerase chain reaction (PCR)based method and were analyzed using an automated DNA analysis method. Results A significant difference in the genotype distribution between OA individuals and controls was observed for IL-10G gene. Individuals with LL genotype were found to have almost 4 times greater possibilily for knee OA than the ones with SS genotype (p = 0.001). OA patients had a significantly higher mean number of CA repeats for IL-10G gene than controls (p = 0.007). No significant differences in allelic frequencies between OA patients and controls were found for IL-10R gene. Conclusion An association between IL-10G microsatellite polymorphisms and idiopathic knee OA was found in subjects of Greek descent

Association of renin-angiotensin system and natriuretic peptide receptor A gene polymorphisms with hypertension in a Hellenic population

Introduction. Hypertension results from the interaction of genetic and environmental factors. Since the renin-angiotensin and the natriuretic peptide systems contribute to blood pressure regulation, variations in the relative genes are candidates for the development of hypertension. Materials and methods. In 194 hypertensives and 304 controls of Hellenic origin, the possible association between the (CA)n repeat polymorphism of angiotensinogen (AGT), the 250 bp insertion/deletion (I/ D) of angiotensin-converting enzyme (ACE), the tetranucleotide repeat polymorphism (TCTG)n of renin, and the (CT)n repeat polymorphism of the natriuretic peptide receptor A (NPRA) and hypertension was assessed. Results. No association between AGT and NPRA polymorphisms and hypertension was observed. The presence of ID or DD genotype of ACE was associated with an increased risk for hypertension compared with the II genotype (OR: 1.782 [95% CI: 1.032-3.077]), whereas the LL genotype of the renin gene was associated with a decreased risk compared with the SS genotype (OR: 0.174 [95% CI: 0.044-0.689]). However, after adjustment for confounding factors only the latter association remained. Conclusions. In the present study conducted in a homogeneous Hellenic population, no associations between AGT, ACE, and NPRA gene polymorphisms and hypertension were found. The presence of a significant negative association between the LL polymorphism of the renin gene and hypertension requires further confirmation. © 2008 SAGE Publications

Polymorphisms of Renin-Angiotensin System and Natriuretic Peptide Receptor A Genes in Patients of Greek Origin with a History of Myocardial Infarction

We assessed the association between (CA)n repeat polymorphism of angiotensinogen (AGT), 250 base pair (bp) insertion/deletion (I/D) of angiotensin-converting enzyme (ACE), tetranucleotide repeat polymorphism (TCTG)n of renin (REN), (CT)n repeat polymorphism of the natriuretic peptide receptor A (NPRA) genes, and the presence and extent of coronary artery disease (CAD) in Greek patients with a history of myocardial infarction (MI). A total of 158 post-MI patients referred for coronary angiography were compared with 144 controls. The SS genotype of the AGT gene was related with an increased risk for 3-vessel CAD (odds ratio [OR], 1.94; 95% confidence interval [CI], 1.05-3.61; P =.041), whereas the SL genotype was related with a decreased risk (OR, 0.44; 95% CI, 0.22-0.87; P =.019). Moreover, there was a trend for the SL genotype of the REN gene toward increased risk for CAD. There was a significant association between (CA)n polymorphism of the AGT gene and the extent of CAD in Greek patients with a history of MI. © 2010, SAGE Publications. All rights reserved

Association of repeat polymorphisms in th estrogen receptors α, β, and androgen receptor genes with knee osteoarthritis

Genetic factors have been shown to play an important role in the etiology of osteoarthritis (OA). To elucidate the possible role of genetic variation in the estrogen receptors α and β (ER-α, ER-β) and androgen receptor (AR) genes with knee OA, the -1174(TA)n, c.1092+3607(CA)n, and c.172(CAG)n repeat polymorphisms of ER-α, ER-β, and AR genes were studied. A case-control cohort of 158 patients with idiopathic knee OA and 193 controls were used. A significant difference was observed in the frequency distribution of -1174(TA)9-25 and c.1092+3607(CA)13-27 repeat polymorphisms of the ER-α and ER-β genes between OA patients and controls (p < 0.005 and p < 0.0001, respectively). A significantly increased odds ratio (OR) for knee OA was observed in individuals having long alleles (LL) genotype for ER-α gene and LL and one short and one long allele (SL) genotypes for ER-β gene compared to individuals with the short alleles (SS) genotype (95% CI 1.03-3.5; p = 0.04 and CI 2.4-8.3 and 2.5-7.5; p < 0.001, respectively). When ORs were adjusted for various risk factors, it was observed that women with LL genotypes for ER-β and AR genes showed significantly increased risk for OA development (p = 0.002 and 0.001). An association between c.1092+3607(CA)13-27 and c.172(CAG)8-34 repeat polymorphisms of the ER-β and AR genes and knee OA was found in individuals of Greek descent. © Blackwell Munksgaard, 2005

Genetic Polymorphisms in the UGT1A1 gene and breast cancer risk in Greek women

Uridine diphospho-glucuronosyltransferase 1 (UGT1A1) is involved in estradiol glucuronidation, which may play a central role in the etiology of breast cancer. A common insertion/ deletion polymorphism in the TATAA-box of the promoter region of UGT1A1 results in decreased initiation of transcription, and has been associated with breast cancer risk in different ethnic groups. In the present study, the role of the above genetic variation at the UGT1A1 locus in breast cancer susceptibility was investigated in a homogeneous population. Our case-control study included 136 women with breast cancer and 186 healthy female controls of Greek origin. The polymorphism A(TA) nTAA in the promoter region of UGT1A1 gene was studied using the Fragment Analysis Software of an automated DNA sequencer and three genotypes (homozygous 7/ 7, heterozygous 6/ 7, and normal homozygous 6/ 6) were identified. No significant associations were observed between the 7/ 7 genotype and breast cancer risk, indicating that further studies in Caucasian women are needed to elucidate the role of UGT1A1 polymorphism in breast cancer risk

Gilbert Syndrome as a Predisposing Factor for Cholelithiasis Risk in the Greek Adult Population

We investigated the hypothesis that coinheritance of the common A(TA)(n)TAA promoter mutation at the UGT1A1 locus associated with Gilbert syndrome is a risk factor for gallstone formation in a homogeneous adult population, by conducting a case-control study that included 198 adult patients with cholelithiasis and 152 healthy controls both of Greek origin. Three genotypes were found: 7/7 (17.8% in controls and 23.3% in patients), 6/7 (33.5% in controls and 46.5% in patients), and normal homozygous 6/6 (48.7% in controls and 30.3% in patients). The Gilbert UGT1A1 genotypes 6/7 and 7/7 show significant association (odds ratio 2.225, 95% confidence interval 1.373-3.605, p = 0.001, and odds ratio 2.101, 95% confidence interval 1.171-3.770, p = 0.013, respectively) with cholelithiasis risk. This association supports the theory that genetic factors are responsible for a fraction of symptomatic gallstone disease; however, further studies are required in different ethnic groups to fully elucidate the involvement of Gilbert syndrome in gallstone disease

Association of repeat polymorphisms in the estrogen receptors alpha, beta (ESR1, ESR2) and androgen receptor (AR) genes with the occurrence of breast cancer

Genetic variation in genes involved in estrogen biosynthesis, metabolism and signal transduction have been suggested to play a role in breast cancer. To determine the possible contribution of genetic variation in the ESR1 (ER-α), ESR2 (ER-β) and AR genes in breast cancer risk the -1174(TA)7-27, c. 1092+3607(CA)10-26 and c. 172(CAG)6-40 repeat variants were studied in a case-control study of 79 women with sporadic breast cancer and 155 controls. No significant difference was observed in the frequency distribution of -1174(TA)7-27 in the ESR1 gene between patients and controls, while a significant difference was observed for repeat polymorphisms c. 1092+3607(CA)10-26 in the ESR2 gene and c. 172(CAG)6-40 in the AR gene (p≤0.0001). A significantly decreased odds ratio (OR) for breast cancer risk was observed in individuals having the LL and the SL genotypes for both the ESR2 (OR=0.010, 95% CI 0.003-0.036, p<0.001; OR=0.013, 95% CI 0.004-0.040, p<0.0001, respectively) and the AR gene (OR=0.040, 95% CI 0.011-0.138, p<0.0001; OR=0.189, 95% CI 0.10-0.359, p<0.0001, respectively), compared to SS genotype. The protective effect of these genotypes remained evident even after adjustment for various risk factors (BMI, age, age at menarche and menopause, family history). In conclusion, an association for breast cancer risk between short (SS) alleles for the repeat variants of the ESR2 and AR genes was found in women of Greek descent. © 2007 Elsevier Ltd. All rights reserved

Genetic polymorphisms in the UDP-glucuronosyltransferase 1A1 (UGT1A1) gene and prostate cancer risk in Caucasian men

Background: Catechol-estrogen metabolites can induce carcinogenesis by acting as endogenous tumor initiators. Glucuronidation, mediated by the UDP-glucuronosyltransferase 1A1 (UGT1A1) enzyme, is a main metabolic pathway of estrogen detoxification in steroid target tissues, such as the prostate. The aim of our study was to investigate the possible correlation between UGT1A1 promoter gene polymorphisms and prostate cancer risk. Patients and methods: 129 patients with prostate cancer and 260 healthy controls were included in our study. A(TA)TAA promoter polymorphism of UGT1A1 gene was studied using the Fragment Analysis Software of an automated DNA sequencer and three genotypes (homozygous 7/7, heterozygous 6/7 and normal homozygous 6/6) were identified. Results: No significant differences were observed between the cancer group and controls regarding the genotyping distribution of the three UGT1A1 promoter genotypes (P > 0.05). Also, no association was found between overall disease risk and the presence of the polymorphic homozygous genotype (TA(7)/TA(7) vs TA(6)/TA(7) + TA(6)/TA(6)) (P = 0.18). In addition, no association was revealed between UGT1A1 genotype distribution and Gleason score (P = 0.55). Conclusion: Our data suggest that the TA repeat polymorphism of UGT1A1 gene does not seem to alter prostate cancer risk susceptibility in Caucasian men. (c) 2010 Elsevier Ltd. All rights reserved

High-Density Lipoprotein in Metabolic Disorders and Beyond: An Exciting New World Full of Challenges and Opportunities

High-density lipoprotein (HDL) is an enigmatic member of the plasma lipid and lipoprotein transport system, best known for its ability to promote the reverse cholesterol efflux and the unloading of excess cholesterol from peripheral tissues. More recently, data in experimental mice and humans suggest that HDL may play important novel roles in other physiological processes associated with various metabolic disorders. Important parameters in the HDL functions are its apolipoprotein and lipid content, further reinforcing the principle that HDL structure defines its functionality. Thus, based on current evidence, low levels of HDL-cholesterol (HDL-C) or dysfunctional HDL particles contribute to the development of metabolic diseases such as morbid obesity, type 2 diabetes mellitus, and nonalcoholic fatty liver disease. Interestingly, low levels of HDL-C and dysfunctional HDL particles are observed in patients with multiple myeloma and other types of cancer. Therefore, adjusting HDL-C levels within the optimal range and improving HDL particle functionality is expected to benefit such pathological conditions. The failure of previous clinical trials testing various HDL-C-raising pharmaceuticals does not preclude a significant role for HDL in the treatment of atherosclerosis and related metabolic disorders. Those trials were designed on the principle of “the more the better”, ignoring the U-shape relationship between HDL-C levels and morbidity and mortality. Thus, many of these pharmaceuticals should be retested in appropriately designed clinical trials. Novel gene-editing-based pharmaceuticals aiming at altering the apolipoprotein composition of HDL are expected to revolutionize the treatment strategies, improving the functionality of dysfunctional HDL