Lack of association between the UDP-glucuronosyltransferase 1A1 (UGT1A1) gene polymorphism and the risk of benign prostatic hyperplasia in Caucasian men.

Glucuronidation, mediated by the UDP-glucuronosyltransferase 1A1 (UGT1A1) enzyme, is an important metabolic process during which steroids are converted to more easily excreted compounds in steroid target tissues, such as the prostate. The aim of our study was to investigate the possible correlation between UGT1A1 promoter gene polymorphism and benign prostatic hyperplasia. 421 blood samples were obtained from 138 consecutive patients diagnosed with benign prostatic hypeplasia (BPH group) and 283 healthy volunteers (control group). A(TA)6TAA 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. No significant differences were observed between the BPH group and controls regarding the genotyping distribution of the three UGT1A1 promoter genotypes (P = 0.39). 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 = 0.31). Our data suggest that the TA repeat polymorphism of UGT1A1 is not associated with increased BPH risk susceptibility in Caucasian men.

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.

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.

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 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.

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.

Absence of linkage to chromosomes 6q and 16p in a Greek population with knee osteoarthritis.

Osteoarthritis (OA) is a common age-related debilitating disease of the joints characterized by degeneration of the articular cartilage which leads to joint pain, discomfort, and immobility. Several risk factors have been associated with OA including a genetic predisposition. Specific chromosomal regions have thus far been associated with susceptibility to OA, the strongest being on chromosomes 2, 6, and 16. We hereby report our data on 34 Central Greek knee OA families that were investigated for linkage to the chromosome 6q and 16p susceptibility regions. All affected members had undergone total knee replacement surgery (TKR) at a single large Orthopedics Unit in Central Greece. Nineteen microsatellite markers were selected, 15 for chromosome 6q and 4 for chromosome 16p at a distance of approximately 7 cm. Allele fragment sizes were determined by an automated DNA sequencer using the Fragment Analysis Software. Our results revealed a statistically significant difference in the ratio of affected females to males with knee OA and also showed that there is no evidence of linkage to regions 6q and 16p in a cohort of Central Greek pedigrees with knee OA.