Department of Molecular Biology and Genetics, and 2Molecular Biology and Biotechnology Research Center, Istanbul Technical University, Istanbul, Turkey. turanlie@itu.edu.tr

OBJECTIVES: To analyse the most common MEFV (Mediterranean fever gene) mutations and polymorphisms in an elderly population free of chronic inflammatory disease (n=164), and explore possible associations between hsCRP (high sensitive C-reactive protein) and RF (rheumatoid factor) levels with MEFV mutations and polymorphisms. METHODS: An elderly group free of chronic inflammatory disease was chosen among the outpatients of the division of geriatric medicine. Total genomic DNA was isolated from blood, and PCR-RFLP analysis was performed using established protocols. Sera were analyzed for hsCRP and RF levels. RESULTS: The frequencies for 694V (1.8%), 694I (1.8%), 680I (0.6%), 726A (2.1%) and 148Q (5%) alleles were found to be similar to Turkish historic controls, with a carrier frequency of 1/4. Further analyses with rheumatoid factor (RF) levels and mutations revealed a significant association between the presence of the E148Q polymorphism with increased RF levels (>15 mg/dl) (xi2= 7.358, p=0.007, OR=5.41 95% CI 1.41-20.64). CONCLUSIONS: Common MEFV mutations and polymorphisms were similarly represented among the elderly population compared to historic controls. On the other hand, a significant association was found between the presence of E148Q polymorphism and increased RF levels. This suggests that the previously noted increased RF levels in elderly populations may somehow be related to the now described association of RF with MEFV E148Q polymorphism.

1Departments of Molecular Genetics and 3Transplantation, Haydarpasa Numune Research and Training Hospital, and 2Department of Basic Sciences, Faculty of Pharmacy, Marmara University, Istanbul, Turkey.

Background: The calcium sending receptor (CaSR) allows parathyroid and kidney tubular cells to regulate PTH secretion and tubular calcium reabsorption. In the present report, we examined the relationship between CaSR gene polymorphisms and parathyroid CaSR expression and serum calcium/parathyroid hormone (PTH) levels and clinical progress in ESRD patients in the Turkish population. Methods: We genotyped the CaSR R990G and Q1011E variants in 192 end-stage renal disease (ESRD) patients by allele-specific PCR. CaSR expression in parathyroid tissues of operated 33 patients was quantified with quantitative reverse transcription-PCR. Results: Compared with other genotypes, the ratio of both codon 990-AA and 1011-CC polymorphisms was found higher in operated patients (p = 0.001). In the total patient group PTH levels were found higher in patients with CC1011 genotype than those with CG1011 (1015.15 +/- 925.41 pg/ml; 523.84 +/- 544.6 pg/ml, respectively, p = 0.002). There were statistically important higher Ca2+ levels in the AA990 allele carrying cases than AG990 positive ones (9.3 +/- 1.0 mg/dl vs. 8.8 +/- 0.9, p = 0.006). On the other hand, the expression of CaSR in parathyroid tissue was found inversely proportional with serum PTH level (r = -0.71). Conclusion: Present data suggest that co-presence of CaSR gene AA990 and CC1011 alleles is a possible risk factor for bad prognosis in secondary hyperparathyroidism. Patients carrying this genotype have tendency to require operation early in their medical therapy period and need postoperative close follow up for possible recurrences.

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.