Polymorphisms in Turkish population

Department of Medical Biology and Genetics, Faculty of Medicine, Gazi University, Besevler, 6500, Ankara, Turkey.

BACKGROUND: Polycystic ovary syndrome (PCOS), whose genetic basis is not completely well understood, is the most common endocrine disorder in women and it typically develops during adolescence. The aim of this study is to investigate the possible association between single nucleotide polymorphisms (SNPs) of FSHR, CYP17, CYP1A1, CAPN10, INSR, SERPINE1 genes and PCOS in adolescent girls. METHODS: DNA samples from forty-four adolescent girls with PCOS and 50 healthy controls were analyzed by PCR-RFLP and direct DNA sequencing to determine the genotypic frequency of 17 different polymorphic loci on the FSHR (A307T, N680S), CYP17 (-34 T/C), CYP1A1 (T6235C), CAPN10 (44, 43, 19, 63), INSR (exon 17 C/T), SERPINE1 (4G/5G) genes. Genotyping of exon 12 (six polymorphisms) and intron 12 (one polymorphism) of INSR gene by direct DNA sequencing was performed for the first time in this study. RESULTS: No significant differences were observed in the genotype and allele distributions of above mentioned polymorphisms between cases and control groups. CONCLUSION: Our data does not support an association between SNPs of FSHR, CYP17, CYP1A1, CAPN10, INSR, SERPINE1 genes and susceptibility to PCOS or related traits in Turkish adolescent girls.

Department of Medical Biology, Faculty of Medicine, Ankara University, Ankara, Turkey guvemg@yahoo.com.

Human P-glycoprotein (P-gp) is encoded by the MDR1 gene, which is located on chromosomal region 7q21 and consists of 28 exons. To date, over 50 single nucleotide polymorphisms (SNPs) have been reported for the MDR1 gene. The effect of these polymorphisms on P-gp function or their clinical impact is in most cases unknown, but some of the SNPs are known to be of functional relevance and can also alter the pharmacokinetics of substrate drugs. The aim of the current study was to analyze for the first time an existing silent MDR1 C1236T (Gly412Gly) polymorphism in a Turkish population. The genotype frequencies of C1236T SNP in a Turkish population were also compared with those in other populations. One hundred unrelated healthy subjects (48 females, 52 males) were included in this study and all them were of Turkish ethnicity. The genotyping of the C1236T SNP was performed by the polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP) method. The frequencies of the wild-type C and mutant T alleles were 45.5 and 54.5%, respectively. The distribution of C1236T genotype frequencies in our study group was found to be similar to that in Czech, Polish, Portuguese, Russian, Malay, and Japanese populations and different from that in French, German, Chinese, and Indian populations. The distributions of CC, CT, and TT genotypes were 20.0, 51.0, and 29.0%, respectively. Our study provides a framework for future studies concerning the role of polymorphic variants of MDR1 gene in the genesis of various diseases or in designing future pharmacogenetic and pharmacokinetic studies conducted with P-gp substrates in the Turkish population.

Gazi University, Faculty of Medicine.

Genetic and environmental factors are involved in Prostate Cancer (PCa) etiology. Single nucleotide polymorphisms (SNPs) may contribute to the PCa pathogenesis. The goal of this study is to determine the role of vitamin D receptor (VDR) gene polymorphisms and haplotypes in the development and progression of sporadic PCa. One hundred and thirty-three PCa patients and one hundred and fifty-seven age-matched healthy controls were genotyped for the ApaI (rs7975232), BsmI (rs1544410) and TaqI (rs731236) polymorphisms in VDR gene by using polymerase chain reaction-restriction fragment length polymorphism. An association was observed between the ApaI polymorphism and PCa predisposition (P = 0.03). When compared with AA genotype, there was a highly notable difference in the frequencies of the Aa (P = 0.02), aa (P = 0.026) and ApaI “a” allele carriers (Aa+aa) (P = 0.009) genotypes. Furthermore, we found a statistical difference in the allele frequencies of the ApaI polymorphism between the sporadic PCa patients and control subjects (P = 0.013). The genotype distribution for the BsmI and TaqI polymorphisms were similar between cases and controls (P >0.05). No clinically significant relationship was found between the three-locus haplotypes and development of sporadic PCa. The genotype frequencies for the three polymorphisms of the VDR gene within subgroups of PCa (defined by tumor stage, Gleason score, PSA levels) were also analyzed, but no statistically noteworthy difference was observed (P >0.05). As far as we know, this is the first study which investigates the relationship between VDR genotypes and sporadic PCa in the Turkish Population. Our findings suggest that the VDR ApaI (rs7975232) polymorphism may play a role in the development of sporadic PCa.