Polymorphisms in Turkish population

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.

Abstract

In this study, we aimed to investigate a possible association of the COX-2 polymorphisms with the risk of developing lung carcinoma. COX-2 (-765G–>C; -1195A–>G) gene polymorphisms were performed by polymerase chain reaction (PCR) and restriction fragment length polymorphism in 118 healthy individuals and 231 patients with lung carcinoma. The present study was the first that addressed the role of the COX-2-765G–>C and -1195A–>G polymorphisms in lung carcinoma in Turkish population. In the present study, we found that the frequencies of GG, CC, and CG genotypes of COX-2-765G–>C and AA, GG, and AG genotypes of -1195A–>G in our control group were 0.22, 0.22, 0.55 and 0.59, 0.0, 0.40, respectively. These frequencies in patient group were 0.34, 0.07, 0.58 and 0.74, 0.04, 0.24, respectively. There were statistically significant differences in COX-2-765G–>C (P = 0.0002) and -1195A–>G genotypes (P = 0.007) between the controls and patients. We found that individuals carrying -765 GG genotype and -765 G allele of COX-2 or 1195 AA genotype of COX-2 and -765G: -1195A haplotype had an increased risk for the development of lung carcinoma. In contrast, individuals with -765 CC, -1195 AG genotypes and -1195 G allele of COX-2 seem to be protective from lung carcinoma. We suggest that the COX-2-765G–>C and -1195A–>G genotypes may be a risk factor for lung carcinoma.