Polymorphisms in Turkish population

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.