Polymorphisms in Turkish population

Curr Med Res Opin. 2011 May 12. [Epub ahead of print]

Canbay E, Cakmakoglu B, Zeybek U, Sozen S, Cacina C, Gulluoglu M, Balik E, Bulut T, Yamaner S, Bugra D.

Source

Basaksehir State Hospital, Department of General Surgery , Basaksehir, Istanbul , Turkey.

Abstract

Abstract Background: There is growing evidence describing DNA repair genes polymorphisms are related to increased cancer risk including colorectal cancer (CRC). The aim of this study was to investigate the associations between the APE1 Asp148Glu, hOGG1 Ser326Cys, XRCC1 Arg399Gln, XRCC3 Thr241Met, XPD Lys751Gln, XPG Asp1104His polymorphisms and CRC risk in Turkish population. Patients and methods: Polymorphisms of APE1 Asp148Glu (rs3136820), hOGG1 Ser326Cys (rs1052133), XRCC1 Arg399Gln(rs25487), XRCC3 Thr241Met (rs861539), XPD Lys751Gln (rs13181), and XPG Asp1104His (rs17655) were determined by polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) methods in blood samples of 79 CRC patients at their initial staging and 247 healthy controls. Of the CRC patients, 26 out of 40 were diagnosed with rectal cancer and received neoadjuvant chemoradiotherapy following diagnosis; 39 others were diagnosed as colon cancer. Results: Our preliminary results showed that frequencies of Glu allele of APE1 Asp148Glu and Cys allele of hOGG1 Ser326Cys were higher in CRC patients than in controls (p = 0.006, OR: 3.43; 95% CI: 1.76-6.70; p = 0.000, OR: 2.77; 95% CI: 1.40-5.48, respectively). Higher frequency of Met allele of XRCC3 Thr241Met was detected in patients treated with neoadjuvant chemoradiotherapy (p = 0.024, OR: 5.25; 95% CI: 1.23-23.39) and with proximal colon tumors (p = 0.04, OR: 2; 95% CI: 1.18-3.34). Increased frequency of Ser/Ser genotype of hOGG1 Ser326Cys was found to be associated both with higher grade (p = 0.001, OR: 6.4; 95% CI: 2.69-62.69) and liver metastasis (p = 0.005, OR: 7.5; 95% CI: 0.7-68.36). Conclusion: APE1 Asp148Glu and hOGG1 Ser326Cys polymorphisms might be associated with increasing risk of CRC in a Turkish population. Future studies with larger-sized samples, as well as detecting the association of DNA repair genes with other confounding factors will help elucidate the exact roles of DNA repair genes polymorphisms in development and progression of CRC.

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.

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

BACKGROUND: Cyclin D1, encoded by the gene CCND1, is a regulatory protein in the cell cycle transition from G(1) phase to S phase. A common polymorphism (A870G) at codon 242 affects splicing of the CCND1 transcript and may cause uncontrollable cellular growth. The present study was performed to test the association between A870G polymorphisms in the CCND1 gene and colorectal cancer risk and progression.

PATIENTS AND METHODS: The 870 A>G polymorphism in the cyclin D1 gene was genotyped in a Turkish colorectal cancer case-control population including fifty-seven cases (35 male, 22 female; mean age + or – SD: 59.33 + or – 13.7 years) and 117 controls (63 male, 54 female; mean age + or – SD: 54.4 + or – 12.2 years) using polymerase chain reaction-restriction fragment length polymorphism analysis.

RESULTS: Genotype frequencies of our patients and controls both confirmed to the Hardy-Weinberg equilibrium. There was no difference in the distribution of CCND1 genotypes and frequencies of the alleles A (59.6% versus 49.6%) and G (40.4% versus 50.4%) in the colorectal cancer patients and controls, respectively. Women homozygous for the cyclin D1 870 GG genotype showed an increased risk for developing colorectal cancer compared to those with the AG+AA genotypes and this result was statistically significant (OR 5.568, 95% CI 1.270-24.417, p=0.02). On the other hand, the cyclin D1 GA genotype was associated with distant metastasis (p=0.016).

CONCLUSION: Our findings suggest that genetic variants of A870G might be associated with distant metastasis and also gender.