Polymorphisms in Turkish population

Ren Fail. 2011;33(5):469-74. Epub 2011 Apr 18.

Reis KA, Ebinç FA, Koç E, Demirci H, Erten Y, Güz G, Derici UB, Bali M, Söylemezoğlu O, Arınsoy T, Sindel S.

Source

Department of Nephrology, Faculty of Medicine, Gazi University , Ankara , Turkey.

Abstract

Background: Diabetic nephropathy (DN) is a leading cause of diabetes-related morbidity and mortality. The aim of this study was to evaluate the relationship of AGT M235T and apoprotein E (APO E) gene polymorphism with DN in Turkish patients of Type 2 diabetes, and to compare genotype and allele distributions among DN patients, non-DN patients, and healthy controls. Methods: AGT M235T and APO E genotype and allele analysis were performed in 111 DN patients, 108 non-DN patients, 106 healthy control subjects for APO E genotype, and 100 for AGT M235T genotype polymorphism. APO E and AGT M235T genotype were determined by RFLP-PCR. Results: The frequencies of APO E ε2/3, ε 3/3, ε 3/4 genotypes were 22.7%, 60%, 60%, respectively, among DN patients and 6.6%, 80%, 10.4%, respectively (p < 0.001), in the non-DN patients. The frequencies of AGT M235T MM, MT, TT genotypes among the same groups were 17%, 46%, 37% and 21%, 63%, 16%, respectively (p < 0.02). Having the ε2/3 genotype and TT genotype increased the risk for DN nephropathy [4.8-fold (95% CI: 1.94-11.67), 2.9-fold (95% CI: 1.27-6.69), respectively]. Conclusion: Our study has shown that AGT M235T TT genotype and APO E ε 2/3 genotype may be linked to a risk for DN among Turkish population.

Abstract

BACKGROUND AND AIMS: Increased synthesis of several urinary proteins including osteopontin (OPN) has been shown to be associated with stone formation within the urinary tract. The objective of this study was to analyze the genotype distributions and allele frequencies for OPN gene promoter T-593A and C6982T (in exon 7) polymorphisms among patients with kidney stones.

METHODS: In this case-control study, the study group consisted of 121 patients with radiologically confirmed nephrolithiasis. Genomic DNA from patients and control cases (n = 100) was analyzed by single-strand conformation polymorphism method and nucleotide sequence analysis.

RESULTS: Homozygous carriers of the T-593T genotype were more frequent, but carriers of the A-593A genotype were less frequent in patients than in controls. There was also an increase in -593T allele (88% in patients vs. 79% in controls) and decrease in -593A allele frequencies (21% in control vs. 12% in patients) in the nephrolithiasis groups (p = 0.013). The carriers of C6982C genotype were less frequent, but marked increases in T6982T genotype (25.6% in patients vs. 7% in controls, p = 0.001) and 6982T allele frequency (53.3% in patients vs. 37.5% in controls, p = 0.001) were noted in patients of Turkish ancestry.

CONCLUSIONS: These results are the first to demonstrate the existence of T-593A promoter polymorphism of the OPN gene and significant association with risk of developing nephrolithiasis. Our results showed marked associations between polymorphisms (C6982T and T-593A) of the OPN gene and the stone-forming phenotypes in the Turkish population.

Abstract

Distribution and prevalence of germline mutations in BRCA1 and BRCA2 differ among different populations. For the Turkish population, several studies have addressed high-risk breast cancer and ovarian cancer (BC-OC) patients. In most studies, both genes were analyzed in part, and a quite heterogeneous mutation spectrum was observed. For high-risk Turkish prostate cancer (PCa) patients, however, there are no data available about mutations of germline BRCA genes. To accurately determine the contribution of germline mutations in BRCA1 and BRCA2 in Turkish BC, OC, and PCa high-risk patients, 106 high-risk BC-OC patients, 50 high-risk PCa patients, and 50 control subjects were recruited. The study represents the only full screening, to date, of a large series of Turkish high-risk BC-OC patients and the only study in Turkish high-risk PCa patients. Mutation screenings were performed on coding exons of both genes with either denaturing gradient gel electrophoresis or denaturing high performance liquid chromatography, or with both techniques. Three deleterious mutations in BRCA1 and three deleterious mutations in BRCA2 were detected in different BC-OC patients, and one truncating mutation was detected in a high-risk PCa patient. In addition, 28 different unclassified and mostly novel variants were detected in both genes, as well as several silent polymorphisms. These findings reflect the genetic heterogeneity of the Turkish population and are relevant to genetic counseling and clinical management.

Abstract

Polymorphisms have been identified in several DNA damage repair genes. These polymorphisms may effect DNA repair capacity and modulate asthma susceptibility. In this study, we aimed to determine the two polymorphisms in DNA repair gene, x-ray repair cross-complementing group 1 (XRCC1), in a sample of Turkish patients with asthma, and evaluate their association with asthma development. We used polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) to analyze XRCC1 Arg194Trp and XRCC1 Arg399Gln polymorphisms in 116 patients with asthma and in 180 disease-free controls. Our data showed a positive association between the polymorphisms of codons 194 (odds ratio [OR] = 1.97, 95% confidence interval [CI] = 1.06-3.66, and p = 0.03 for Arg/Trp genotype) and 399 (OR = 1.87, 95% CI = 1.12-3.13, and p = 0.02 for Arg/Gln genotype, and OR = 2.59, 95% CI = 1.24-5.43, and p = 0.01 for Gln/Gln genotype) and asthma risk. No statistically significant difference was found for the allelic and genotypic distributions of the polymorphisms in XRCC1 gene between mild and moderate asthmatic patients. A combined analysis of the effect of XRCC1 codons 194 and 399 revealed the highest risk (OR = 4.17, 95% CI = 1.77-9.83, and p = 0.001) for carriers of the polymorphic alleles in both of these codons. These results suggest that the risk of asthma may be associated with DNA repair mechanisms, and understanding these mechanisms will help identify individuals at increased risk of developing asthma and should lead to improved treatment of asthma.