GSTM1 Copy Number Is Not Associated With Risk of Kidney Failure in a Large Cohort
GSTM1 Copy Number Is Not Associated With Risk of Kidney Failure in a Large Cohort
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DOI：
10.3389/fgene.2019.00765
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发表时间：
2019-08-30
影响因子：
3.7
通讯作者：
Lee, Ming Ta Michael
中科院分区：
文献类型：
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作者：
Zhang, Yanfei;Zafar, Waleed;Lee, Ming Ta Michael
谷胱甘肽S转移酶MU1基因缺失在人群中很常见，一些研究表明它与慢性肾脏疾病的进展有关。需要验证该关联。我们使用DiscovEHR队列中的整个外显子组测序数据估计了GSTM1拷贝数。肾衰竭被定义为需要透析或接受肾移植，使用电子健康记录中的数据并连接到美国肾脏数据系统，或最新的EGFR<；15ml/min/1.73m(2)。在46,983名无关参与者的队列中，28.8%的黑人和52.1%的白人携带0拷贝的GSTM1。在平均9.2年的随访中，在46,187名白人参与者中观察到645起肾衰竭事件，在796名黑人参与者中观察到28起。在对年龄、性别、体重指数、吸烟状况、遗传主成分或合并疾病(高血压、糖尿病、心力衰竭、冠状动脉疾病和中风)进行校正的COX回归分析中，无论采用基因分型、显性模型还是隐性模型，GSTM1拷贝数与肾衰竭均无显著关联。在敏感性分析中，GSTM1拷贝数与基线年龄在45岁或以上、基线EGFR为60ml/min/1.73m(2)、或基线年份在1996至2002年之间的受试者的肾衰竭无关。总而言之，在一项大型队列研究中，我们没有发现GSTM1拷贝数与肾衰竭之间的关联。
Deletion of glutathione S-transferase mu 1 (GSTM1) is common in populations and has been asserted to associate with chronic kidney disease progression in some research studies. The association needs to be validated. We estimated GSTM1 copy number using whole exome sequencing data in the DiscovEHR cohort. Kidney failure was defined as requiring dialysis or receiving kidney transplant using data from the electronic health record and linkage to the United States Renal Data System, or the most recent eGFR < 15 ml/min/1.73 m(2). In a cohort of 46,983 unrelated participants, 28.8% of blacks and 52.1% of whites had 0 copies of GSTM1. Over a mean of 9.2 years follow-up, 645 kidney failure events were observed in 46,187 white participants, and 28 in 796 black participants. No significant association was observed between GSTM1 copy number and kidney failure in Cox regression adjusting for age, sex, BMI, smoking status, genetic principal components, or comorbid conditions (hypertension, diabetes, heart failure, coronary artery disease, and stroke), whether using a genotypic, dominant, or recessive model. In sensitivity analyses, GSTM1 copy number was not associated with kidney failure in participants that were 45 years or older at baseline, had baseline eGFR < 60 ml/min/1.73 m(2), or with baseline year between 1996 and 2002. In conclusion, we found no association between GSTM1 copy number and kidney failure in a large cohort study.