Polymorphisms in Turkish population

Sections of Periodontology and Oral Biology, College of Dentistry, The Ohio State University Health Sciences Center, Columbus, OH 43218-2357, USA.

BACKGROUND: Neutrophil formylpeptide receptors (FPRs) play an important role in bacterial recognition and chemotaxis. Defective FPR1 expression and impaired polymorphonuclear leukocyte chemotaxis toward bacterial formylpeptides are associated with aggressive periodontitis (AgP). The objective of this study was to determine whether single nucleotide polymorphisms (SNPs) in FPR1 are associated with AgP. METHODS: Genomic DNA was isolated from blood samples obtained from African Americans (30 subjects with AgP and 33 healthy controls) and Turks (75 subjects with AgP and 63 healthy controls). A highly polymorphic fragment of the FPR1 gene was amplified by polymerase chain reaction and sequenced for analysis of SNPs. RESULTS: Five previously identified SNPs were detected in African Americans, whereas six were detected in Turkish subjects. The frequency of synonymous SNP c.348T>C was significantly higher in African Americans with AgP than in controls (P = 0.029). The 348T allele was significantly associated with AgP (P = 0.010). Seven of the subjects with AgP, but none of the controls, were homozygous for 348T. FPR1 haplotypes 348T.568A, 348T.576T, and 348T.568A.576T were significantly increased in African Americans with AgP (P <0.02). The Turkish population did not exhibit significant differences in FPR1 SNP frequencies between subjects with AgP and controls. CONCLUSIONS: FPR1 SNP c.348T>C is associated with AgP in African Americans. Individuals who are homozygous for 348T may have an increased risk for developing this disorder.

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.