The Loss of GSTM1 Associates with Kidney Failure and Heart Failure
The Loss of GSTM1 Associates with Kidney Failure and Heart Failure
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DOI：
10.1681/asn.2017030228
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发表时间：
2017-11-01
影响因子：
13.6
通讯作者：
Grams, Morgan E.
中科院分区：
文献类型：
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作者：
Tin, Adrienne;Scharpf, Robert;Grams, Morgan E.
谷胱甘肽S-转移酶mu 1（GSTM 1）编码一种酶，催化亲电子化合物与谷胱甘肽的结合，以促进其降解或排泄。GSTM 1的一个或两个拷贝的丢失在许多人群中很常见，并且与CKD进展相关。基于GSTM 1缺失也与肾衰竭和心力衰竭相关的假设，我们在社区动脉粥样硬化风险（ARIC）研究（一项白色和黑人参与者的基于社区的前瞻性队列研究）中使用外显子组测序读数估计了GSTM 1拷贝数。总体而言，51.2%和39.8%的白色参与者和25.6%和48.5%的黑人参与者分别有0或1个GSTM 1拷贝。在24.6年的平均随访中，5715名无肾衰竭的参与者发生了256起肾衰竭事件，5368名无心力衰竭的参与者发生了1028起心力衰竭事件。在调整人口统计学、糖尿病和高血压的分析中，GSTM 1的零或一个拷贝与肾衰竭和心力衰竭的高风险相关（GSTM 1的零或一个拷贝与两个拷贝的校正风险比[95%置信区间]：肾衰竭，1.66 [1.27至2.17];心力衰竭，1.16 [1.04至1.29]）。GSTM 1基因拷贝数为0和1的受试者之间的风险无显著差异（P > 0.10）。总之，GSTM 1的丢失与肾衰竭和心力衰竭的发生显著相关，与传统的危险因素无关。这些结果表明GSTM 1功能是预防肾衰竭和心力衰竭的潜在治疗靶点。
Glutathione S-transferase mu 1 (GSTM1) encodes an enzyme that catalyzes the conjugation of electrophilic compounds with glutathione to facilitate their degradation or excretion. The loss of one or both copies of GSTM1 is common in many populations and has been associated with CKD progression. With the hypothesis that the loss of GSTM1 is also associated with incident kidney failure and heart failure, we estimated GSTM1 copy number using exome sequencing reads in the Atherosclerosis Risk in Communities (ARIC) Study, a community- based prospective cohort of white and black participants. Overall, 51.2% and 39.8% of white participants and 25.6% and 48.5% of black participants had zero or one copy of GSTM1, respectively. Over amedian follow-up of 24.6 years, 256 kidney failure events occurred in 5715 participants without prevalent kidney failure, and 1028 heart failure events occurred in 5368 participants without prevalent heart failure. In analysis adjusted for demographics, diabetes, and hypertension, having zero or one copy of GSTM1 associated with higher risk of kidney failure and heart failure (adjusted hazard ratio [95% confidence interval] for zero or one versus two copies of GSTM1: kidney failure, 1.66 [1.27 to 2.17]; heart failure, 1.16 [1.04 to 1.29]). Risk did not differ significantly between participants with zero and one copy of GSTM1 (P > 0.10). In summary, the loss of GSTM1 was significantly associated with incident kidney and heart failure, independent of traditional risk factors. These results suggest GSTM1 function is a potential treatment target for the prevention of kidney and heart failure.