A986S polymorphism of the calcium-sensing receptor and circulating calcium concentrations

被引:142
作者
Cole, DEC
Peltekova, VD
Rubin, LA
Hawker, GA
Vieth, R
Liew, CC
Hwang, DM
Evrovski, J
Hendy, GN
机构
[1] Univ Toronto, Dept Lab Med & Pathobiol, Toronto, ON, Canada
[2] Univ Toronto, Dept Med, Toronto, ON, Canada
[3] Univ Toronto, Dept Genet, Toronto, ON, Canada
[4] McGill Univ, Dept Med Physiol & Human Genet, Montreal, PQ, Canada
基金
英国医学研究理事会;
关键词
D O I
10.1016/S0140-6736(98)06434-4
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Background The regulation of extracellular calcium concentration by parathyroid hormone is mediated by a calcium-sensing, G-protein-coupled cell-surface receptor (CASR). Mutations of the CASR gene alter the set-point for extracellular ionised calcium [Ca2+](o) and cause familial hypercalcaemia or hypocalcaemia. The CASR missense polymorphism, A986S, is common in the general population and is, therefore, a prime candidate as a genetic determinant of extracellular calcium concentration. Methods We genotyped the CASR A986S variant (S allele frequency of 16.3%) in 163 healthy adult women and tested samples of their serum for total calcium, albumin, total protein, creatinine, phosphate, pH, and parathyroid hormone. A prospectively generated, random subset of 84 of these women provided a whole blood sample for assay of [Ca2+](o). Findings The A986S genotype showed no association with total serum concentration of calcium, until corrected for albumin. In a multivariate regression model, biochemical and genetic variables accounted for 74% of the total variation in calcium. The significant predictors of serum calcium were: albumin (p<0.001), phosphate (p=0.02), parathyroid hormone (p=0.007), pH (p=0.001), and A986S genotype (p=0.009). Fasting whole-blood [Ca2+](o) also showed an independent positive association with the 986S variant (p=0.013). Interpretation The CASR A986S variant has a significant effect on extracellular calcium. The CASR A986S polymorphism is a likely candidate locus for genetic predisposition to various bone and mineral disorders in which extracellular calcium concentrations have a prominent part.
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收藏
页码:112 / 115
页数:4
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