Association between total serum calcium and the A986S polymorphism of the calcium-sensing receptor gene
Association between total serum calcium and the A986S polymorphism of the calcium-sensing receptor gene
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DOI：
10.1006/mgme.2000.3126
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发表时间：
2001-02-01
影响因子：
3.8
通讯作者：
Rubin, LA
中科院分区：
文献类型：
--
作者：
Cole, DEC;Vieth, R;Rubin, LA
血清钙受到严格的生理控制，但它也是具有显着遗传调控的数量性状。 CASR 基因突变会导致家族性低尿钙性高钙血症或常染色体显性甲状旁腺功能减退症，具体取决于它们是否分别减少或增加配体与受体蛋白的结合。我们描述了离子钙与该 G 蛋白偶联受体细胞质尾部发现的常见多态性 (A986S) 之间的关联。我们在此报告一项针对 387 名健康年轻女性的独立研究。通过等位基因特异性扩增进行基因分型，并通过自动临床测定测量血清化学成分。 SS、AS 和 AA 基因型的频率分别为 6、107 和 274，产生 986S 等位基因频率为 15.4%。 SS 组（9.88 +/- 0.29 mg/dL，P = 0.015）和 AS 组（9.45 +/- 0.05 mg/dL，P = 0.002）的平均总血清钙（Ca-T）显着高于 AA 组（9.23 +/- 0.04 mg/dL）。在多元回归模型中，当包括血清白蛋白、球蛋白、无机磷酸盐和肌酐协变量时，A986S 基因型仍然是 Ca-T 的独立显着预测因子 (P < 0.0001)。这些数据首次显示了常见的多态性与血清电解质浓度之间的显着关联。 A986S 多态性也是骨和矿物质代谢紊乱的潜在诱发因素。 (C) 2001 年学术出版社。
Serum calcium is under tight physiological control, but it is also a quantitative trait with substantial genetic regulation. Mutations of the CASR gene cause familial hypocalciuric hypercalcemia or autosomal dominant hypoparathyroidism, depending on whether they decrease or increase, respectively, ligand binding to the receptor protein. We described an association between ionized calcium and a common polymorphism (A986S) found in the cytoplasmic tail of this G protein-coupled receptor. We report here on an independent study of 387 healthy young women. Genotyping was performed by allele-specific amplification and serum chemistries were measured by automated clinical assay. Frequencies of SS, AS, and AA genotypes were 6, 107, and 274, respectively, yielding a 986S allele frequency of 15.4%. Mean total serum calcium (Ca-T) was significantly higher in the SS (9.88 +/- 0.29 mg/dL, P = 0.015) and AS groups (9.45 +/- 0.05 mg/dL, P = 0.002), than in the AA group (9.23 +/- 0.04 mg/dL). In multiple regression modeling, the A986S genotype remained an independently significant predictor of Ca-T (P < 0.0001) when serum albumin, globulin, inorganic phosphate, and creatinine covariates were included. These data are the first to show significant association between a common polymorphism and concentrations of a serum electrolyte. The A986S polymorphism is also a potential predisposing factor in disorders of bone and mineral metabolism. (C) 2001 Academic Press.