A Functional Common Polymorphism of the ABCB1 Gene Is Associated With Chronic Kidney Disease and Hypertension in Chinese
A Functional Common Polymorphism of the ABCB1 Gene Is Associated With Chronic Kidney Disease and Hypertension in Chinese
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ABCB1 基因的功能性常见多态性与中国人的慢性肾病和高血压相关
DOI：
10.1093/ajh/hpt126
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发表时间：
2013-12-01
影响因子：
3.2
通讯作者：
Wang, Ji-Guang
中科院分区：
文献类型：
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作者：
Liu, Ming;Li, Yan;Wang, Ji-Guang
通透性糖蛋白由atp结合盒B1基因（ABCB1）编码，是肾脏中有毒代谢物的挤压者。人类ABCB1基因的一种功能性共同多态性（C3435T, rs1045642）已被发现与肾移植患者的同种异体移植结果相关。在这项研究中，我们调查了2个中国人群中C3435T多态性与肾功能和血压（BP）的关系。方法分别从山区（浙江省）和新城市化郊区（上海市）招募发现人群和复制人群。我们使用ABI SNapShot方法对所有受试者进行基因分型。慢性肾脏疾病（CKD）定义为肾小球滤过率= 30mg。结果在1987名受试者的发现人群中，调整协变量后，TT纯合性（n = 217）与较高的CKD风险相关(n = 369，优势比(OR) = 1.73；P = 0.003)，收缩压升高（+3.1 mm Hg, P = 0.03），脉压升高（+3.4 mm Hg, P = 0.001）。这些相关性依赖于年龄（P-int = 60岁（n = 374））， CKD相应的OR或差异为2.40，收缩压为15.1 mm Hg，脉压为12.4 mm Hg （P < 0.001）。在2427名老年（60岁）受试者的类似调整分析中，TT纯合性也与CKD的高风险相关（OR = 1.39; P = 0.02），高血压与CKD的相关性增强（OR = 1.50; P = 0.04）。结论ABCB1 C3435T多态性可能预测CKD，尤其是老年人。
BACKGROUNDPermeability glycoprotein is encoded by the ATP-binding cassette B1 gene (ABCB1) and is an extruder of toxic metabolites in the kidney. A functional common polymorphism (C3435T, rs1045642) in the human ABCB1 gene has been found to be associated with allograft outcome in kidney transplant patients. In this study, we investigated the association of the C3435T polymorphism with renal function and blood pressure (BP) in 2 Chinese populations.METHODSThe discovery and replication populations were recruited from a mountainous area (Zhejiang Province) and a newly urbanized suburban area (Shanghai), respectively. We genotyped all subjects using the ABI SNapShot method. Chronic kidney disease (CKD) was defined as an estimated glomerular filtration rate = 30 mg.RESULTSIn the discovery population of 1,987 subjects, after adjustment for covariables, TT homozygosity (n = 217) was associated with a higher risk of CKD (n = 369; odds ratio (OR) = 1.73; P = 0.003) and with higher systolic BP (+3.1 mm Hg; P = 0.03) and pulse pressure (+3.4 mm Hg; P = 0.001). These associations were dependent on age (P-int = 60 years (n = 374), the corresponding OR or difference was 2.40 for CKD, 15.1 mm Hg for systolic BP, and 12.4 mm Hg for pulse pressure (P < 0.001). In similar adjusted analyses in the replication population of 2,427 elderly (= 60 years) subjects, TT homozygosity was also associated with a higher risk of CKD (OR = 1.39; P = 0.02) and an enhanced association of hypertension with CKD (OR = 1.50; P = 0.04).CONCLUSIONSThe ABCB1 C3435T polymorphism might predict CKD, especially in the elderly.