Clin Exp Hypertens. 2011;33(3):202-8. Epub 2011 Apr 8.

Cabadak H, Orun O, Nacar C, Dogan Y, Guneysel O, Fak AS, Kan B.

Source

Department of Biophysics, Marmara University School of Medicine, Istanbul, Turkey.

Abstract

Hypertension is a multifactorial disorder that constitutes a major risk factor for the cardiovascular system. Heterotrimeric G-proteins, which couple receptors for diverse extracellular enzymes or ion channels, are correlated with disease mechanisms. Several studies have demonstrated an association between G protein polymorphisms and essential hypertension in some populations, although contradictive results also exist. In this study, we have investigated the potential role of the C825T, C1429T, and G5177A polymorphisms of the β3 subunit of G-proteins in essential hypertension in a group of Turkish subjects. Genomic DNA from 106 normotensive individuals (117.4 ± 13.1, 75.2 ± 10.5; systolic blood pressure (SBP) and diastolic blood pressure (DBP) levels, respectively) and 101 hypertensive subjects (152.3 ± 18.0, 92.5 ± 11.6; SBP and DBP levels, respectively) were studied by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and direct sequencing methods for these polymorphisms. Allele frequencies of the polymorphisms were consistent with Hardy Weinberg equilibrium, except for the C825T polymorphism (χ(2) = 7.8). The frequencies of the 825T and 1429T variants were higher in hypertensive subjects compared to those of controls. Differences between hypertensives and controls were not statistically significant, though difference was very close to significance for C825T (p = 0.056 and 0.099 for 825T and 1429T, respectively). T allele frequency in overall population showed significant association with hypertension for C825T (0.0134). The prevalence of the 5177A-variant was very low and all subjects carrying it were heterozygotes in both groups.

Mol Med Report. 2010 Jul-Aug;3(4):723-7. doi: 10.3892/mmr_00000324.

Pinarbasi H, Silig Y, Pinarbasi E.

Source

Department of Biochemistry, Faculty of Medicine, Cumhuriyet University, 58140 Sivas, Turkey. hpinar2658@gmail.com.

Abstract

Microsomal epoxide hydrolase plays a dual role in the activation and detoxification of carcinogenic compounds. Two polymorphic sites have been described in exons 3 and 4 of the microsomal epoxide hydrolase gene that change tyrosine residue 113 to histidine (Tyr113His) and histidine 139 to arginine (His139Arg), respectively. The exon 3 polymorphism reduces enzyme activity by approximately 50%, whereas the exon 4 polymorphism causes a 25% increase in activity. In the present study, the distribution of these polymorphisms in a Turkish population including 625 unrelated healthy individuals was examined using a PCR-RFLP method. The observed genotype frequencies of microsomal epoxide hydrolase exon 3 were 54, 38 and 8% for Tyr113Tyr, Tyr113His and His113His, respectively. Exon 4 genotype frequencies were found to be 69, 29 and 2% for His139His, His139Arg and Arg139Arg, respectively.

Abstract

BACKGROUND: Breast cancer (BC), is more prevalent in subjects who have had prolonged exposure to heterocyclic amines, aromatic amines and high levels of oestradiol. Cytochrome P450 1B1 (CYP1B1) and N-acetyltransferase2 (NAT2) have complementary role in metabolism of xenobiotics such as arylamines and heterocyclic amines, CYP1B1 also hyroxylates 17-beta oestradiol. CYP1B1*3 polymorphism and seven missense and four silent polymorphisms of NAT2 were investigated.

PATIENTS AND METHODS: Sixty Turkish female BC patients and 103 healthy controls were phenotyped by polymerase chain reaction (PCR) based restriction fragment length polymorphism (RFLP). Results and

CONCLUSION: The distribution of NAT2 activity in the healthy control group was found to be correlated with that of healthy caucasians. Patients had slow acetylator phenotypes of NAT2, 1.8 times higher than controls but no statistical differences were found (p=0.07). In addition, the NAT2*5 alelle was more statistically correlated with breast cancer patients rather than the controls (p=0.02). Moreover, NAT2*5B was the most frequent haplotype of the NAT2*5 family (p=0.000). Breast cancer patients were detected to posses more CYP1B1*3 mutant alleles than the controls (p=0.043). The combined effect of CYP1B1*3 polymorphism and NAT2 slow acetylator genotype contributed to an increased risk for breast cancer in patients in this study (p=0.004).

Abstract

The -219G/T (rs405509) and +113G/C (rs440446) polymorphisms within the regulatory region of the apolipoprotein E (APOE) gene have been related to the transcriptional activity of the gene. We examined the effect of the stated polymorphisms and their construct haplotypes with the APOE varepsilon2/varepsilon3/varepsilon4 polymorphism on lipid levels and insulin resistance in the Turkish Adult Risk Factor Study. Randomly selected 1774 adults (mean age, 55.0 +/- 11.7 years; 51.2% women) participating in the population-based Turkish Adult Risk Factor Study were cross-sectionally analyzed for the -219G/T, +113G/C, and varepsilon2/varepsilon3/varepsilon4 polymorphisms as well as their haplotypes. Insulin resistance was defined as the 70th percentile in the sample (>2.51) of the homeostatic model assessment (HOMA). The frequencies of the -219T and +113C alleles were 0.477 and 0.423, respectively; and those of haplotype 1 (GGvarepsilon3) and haplotype 2 (TCvarepsilon3) were 44.1% and 41.9%, respectively. The -219G/T and +113G/C genotypes (both P < .04) and diplotypes of haplotype 2 (TCvarepsilon3) (P < .014) were inversely related to serum fasting insulin and the HOMA index, even after controlling for 8 relevant covariates, but not to serum lipids. Within the APOE3 group, haplotype 2 (TC-/TC+) heterozygotes had an odds ratio of 0.66 (95% confidence interval, 0.42-0.99) for HOMA of insulin resistance after adjusting for 8 covariates. APOE promoter polymorphisms and their diplotypes are independently related with serum fasting insulin levels and HOMA index among Turks.