维生素D受体基因多态性与特发性甲状旁腺功能减退症的相关性  

Association of vitamin D receptor gene polymorphisms with idiopathic hypoparathyroidism phenotypes

作　　者：全婷婷[1] 聂敏[1] 李悦芃[1] 姜艳[1] 李梅[1] 夏维波[1] 孟迅吾[1] 邢小平[1] 王鸥[1] 

机构地区：[1]中国医学科学院 北京协和医学院 北京协和医院内分泌科,100730

出　　处：《中华医学杂志》2017年第36期2833-2838,共6页National Medical Journal of China

基　　金：国家自然科学基金（81270873,81100559）;国家临床重点专科建设项目（WBYZ2011-873）

摘　　要：目的探讨维生素D受体（VDR）基因多态性与特发性甲状旁腺功能减退症（IHP）发病及临床表型间的相关性。方法纳入1987年12月至2015年12月于北京协和医院内分泌科门诊就诊的IHP共203例作为病例组，年龄及性别匹配的209名健康人作为对照组，通过Sequenom Mass Array方法检测VDR基因rs739837、rs3847987、rs2228570位点的基因分型，计算等位基因和基因型分布频率，分析其与IHP发病的相关性。在IHP患者中比较各SNP位点不同基因型的临床特点及生化指标，以探索上述不同SNPs分型与IHP临床表型的关系，并在接受普通维生素D治疗的IHP患者中比较不同基因型间治疗效果的差异。结果病例组与对照组的VDR基因上述SNP位点基因型及等位基因频率分布差异均无统计学意义（均P〉0．05）。但在初治IHP患者中，rs739837基因型与血钙水平相关（r=0．186，P=0．026）；且rs2228570位点的GG基因型患者接受普通维生素D联合钙剂治疗后的24h尿钙水平较GA及AA基因型者升高（277．7mg比141．1mg，P=0．024）。结论VDR基因的rs739837、rs3847987和rs2228570功能性SNP位点可能与IHP发病无关，但rs739837基因型与血钙水平相关，VDR基因rs2228570多态性可能对IHP维生素D制剂治疗效果存在影响。Objective To explore the association of vitamin D receptor （VDR） gene polymorphisms with idiopathic hypoparathyroidism （IHP）. Methods Two hundred and three patients with IHP and 209 healthy age- and sex-matched subjects were recruited at Peking Union Medical College Hospital between December 1987 and December 2015 as case group and control group, respectively. The VDR gene polymorphisms including rs739837, rs3847987 and rs2228570 were analyzed by Sequenom Mass Array. The frequency of different genotypes and alleles was detected, then their association with pathogenesis of IHP was analyzed. The clinical characteristics, biochemical indicators were collected to explore the genotype- phenotype relationship. The role of reactions to vitamin D treatment were compared between patients with different genotypes. Results There was no significant difference in the genotypes and allele frequency distribution of SNPs between the two groups （all P 〉 0. 05）. However, in the initially-treated patients, the genotypes of rs739837 were related to serum calcium level （r = 0. 186,P = 0. 026）. And patients with GG genotype of rs2228750 had higher level of urine calcium than GA and AA （ 277.7 mg vs 141.1 mg, P = 0. 024） after treating with oral vitamin D3 and calcium. Conclusions Functional SNPs of VDR gene including rs739837, rs3847987 and rs2228570 might be irrelevant to the pathogenesis of IHP. But the genotypes of rs739837 were related to serum calcium level, and rs2228570 may have an effect on the different responses to vitamin D and its analogues in IHP patients.

关 键 词：受体 骨化三醇 多态性 单核苷酸 甲状旁腺功能减退症 

分 类 号：R582.2[医药卫生—内分泌]