Purpose: Two single nucleotide polymorphisms (SNPs), R990G and A986S of the CaSR gene have been shown to influence response of PTH. The aim of this study was to establish an association between CaSR polymorphisms, PTH and calcium levels in females with vitamin D deficiency (VDD).
Methods: A cross sectional study was conducted at Aga Khan University. Adult females (n=141) with known VDD, iPTH and calcium levels were recruited. CaSR polymorphisms were analyzed by RFLP-PCR. We looked for A986S and R990G SNPs.
Results: The study participants had mean age of 31±8.2 years, mean iPTH 96.2±66 pg/ml, mean 25OHD 8.4±7.7 ng/ml and calcium of 9±0.58 mg/dl. The frequency for R990G polymorphism (AA, AG, GG) was 80%, 8.9% and 11.1%, whereas for A986S (GG, GT, TT) was 68%, 25% and 7%. The serum PTH levels were higher in GG genotype (148.65 vs. 91.47 and 86.1 pg/ml, p value 0.008) and lower calcium levels (8.4 vs. 9, p value 0.002). On the contrary, association of A986S polymorphism with serum PTH, or calcium levels was not observed in the present study. On haplotypes analysis PTH levels were significantly higher in individuals carrying G:G Haplotype (36.7 pg/ml, P_ 0.0048) when compared with A:G haplotype subjects. Serum calcium concentration was significantly lower in individuals carrying the haplotype G:T (0.51 mg/dl, P_0.0079) than in those carrying haplotype A:G.
Conclusions: Patients with vitamin D deficiency bearing the GG genotype of R990G SNP, have higher plasma PTH levels and lower serum calcium and Haplotype G:G and G:T are significantly associated with higher PTH and lower calcium levels respectively
Keywords: Vitamin D deficiency (VDD), Calcium sensing receptor (CaSR), Single nucleotide polymorphisms, Pakistan
Available at: http://works.bepress.com/aysha_habib/9/