Polymorphisms in Turkish population

Department of Endocrinology and Metabolism Disease, Ege University Medical School, Bornova, Izmir, Turkey. drmerdogan61@yahoo.com

OBJECTIVE: Interleukin-10 (IL-10) is a major anti-inflammatory cytokine that plays a crucial role in the regulation of the immune system. Chronic inflammation has been reported to be a risk factor for thyroid neoplasia. The propensity to mount an inflammatory response is modified by germ line variation in cytokine and other inflammation-related genes. We hypothesized that a proinflammatory genotype would be positively associated with thyroid cancer. We aimed to evaluate the relation between the genotypic and allelic frequencies of the IL-10(-1082 G/A), IL-10(-592 A/C), and IL-10(-819 C/T) polymorphisms, and their association with the risk of developing papillary thyroid cancer (PTC) in the Turkish population. RESEARCH DESIGN AND METHODS: Forty-two patients with PTC and 113 healthy controls were included in this study. The diagnosis of PTC was confirmed by histopathologic examination after surgery. The evaluation of genotype for IL-10 gene polymorphism was performed using PCR-restriction fragment length polymorphism method. RESULTS: Statistically significant difference IL-10(-1082 G/A) gene polymorphism was determined between 2 (PTC and control) groups. No difference was determined with respect to IL-10(-592 A/C) and IL-10(-819 C/T) gene polymorphisms, and IL-10(-1082 G/A), IL-10(-592 A/C), and IL-10(-819 C/T) allele frequencies of participating between the control group and the patients with PTC (p>0.05). CONCLUSIONS: The polymorphism of IL-10(-1082 G/A) gene was significantly associated with the occurrence of PTC. Such studies will contribute significantly to our understanding of the biological role of IL-10(-1082 G/A) gene polymorphism in PTC development. In conclusion, IL-10(-1082 G/A) gene polymorphism may affect the survival of papillary thyroid carcinoma.

Institute of Clinical Pharmacology, Charité-Universitätsmedizin Berlin, Humboldt University of Berlin, Schumannstrasse 20/21, 10098 Berlin, Germany.

BACKGROUND: OATP1B1 is one of the key hepatocellular uptake transporters providing extraction of diverse compounds, including bile acids, xenobiotics, and a variety of drugs, from portal venous blood into the liver. Polymorphisms of the SLCO1B1 gene have been demonstrated to influence in vitro transport function and the pharmacokinetic profile of compounds. OBJECTIVE: The goal of our study was the comparison of SLCO1B1 gene sequence variability in three ethnic groups as a basis for future genetic association studies. METHODS: Eighteen exonic SLCO1B1 single nucleotide polymorphisms (SNPs) were genotyped by PCR and RFLP analysis in 300 German, 94 Turkish, and 115 African subjects. Calculation of pairwise linkage disequilibrium and estimation of population haplotype frequencies were carried out, and haplotype block structure was determined. RESULTS: Only eight genotyped SNPs (c.388A>G, c.411G>A, c.463C>A, c.521T>C, c.571C>T, c.597C>T, c.1463G>>C, c.1929A>C) were found in at least one of our German, Turkish, or African samples. A total of 12 haplotypes with a frequency >or=1% in at least one of the three populations could be inferred. Between the Caucasian and African samples, significant differences in sequence variability were observed leading to a different haplotype profile in these populations. CONCLUSION: Our results demonstrate a high sequence variability of OATP1B1 within different popuations. In the future, distinct haplotypes should be taken into account when studying the effect of OATP1B1 on drugs in different populations.

Department of Cardiology, Ege University School of Medicine, Izmir, Turkey.

Introduction: Idiopathic ventricular arrhythmias commonly refer to ventricular tachycardia (VT) and/or frequent/monomorphic premature ventricular contractions (PVC) in patients with structurally normal heart. Activation of sympathetic tone has been shown to play an important role in the provocation and maintenance of these arrhythmias. We investigated whether common single nucleotide polymorphisms in the beta(1) and beta(2)-adrenergic receptors are associated with idiopathic ventricular arrhythmias. Methods: A total of 143 unrelated patients presenting with idiopathic ventricular arrhythmias were prospectively included in a case-control association study. Patient population was matched by age and gender to the unrelated, healthy control subjects (N = 307). All study subjects were of Turkish (Anatolian Caucasian) descent. Allele and genotype frequencies of the Gly389Arg and Ser49Gly polymorphisms of the beta(1)-adrenergic receptor and Arg16Gly, Gln27Glu, and Thr164Ile polymorphisms of the beta(2)-adrenergic receptor were compared between patient population and control subjects. The genotype frequencies were in Hardy-Weinberg equilibrium. Results: Patients with idiopathic ventricular arrhythmias had higher frequency of Arg389Arg genotype (22.4% vs 1.6%, P < 0.001), Arg389Gly49 (5.24% vs 0.73%, P = 0.005), and Arg389Ser49 (36.7% vs 13.6%, P < 0.001) haplotypes of the beta(1)-adrenergic receptor, and higher frequency of Gly16Gly (31.5% vs 13.4%, P < 0.001), Glu27Glu genotypes (18.2% vs 10.1%, P = 0.006) and Gly16Gln27Thr164 (15.3% vs 7.4%, P = 0.002), Gly16Glu27Thr164 (13.1% vs 7%, P = 0.004), and Gly16Glu27Ile164 (13.2% vs 6%, P = 0.002) haplotypes of the beta(2)-adrenergic receptor compared to control subjects. Conclusion: Our data suggest that common single nucleotide polymorphisms in the beta(1) and beta(2)-adrenergic receptors are significantly associated with idiopathic ventricular arrhythmias in Turkish population.