The Loss of Associates with Kidney Failure and Heart Failure

Glutathione S-transferase mu 1 ( 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 is common in many populations and has been associated with CKD progression. With the hypothesis that the loss of is also associated with incident kidney failure and heart failure, we estimated 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 , respectively. Over a median 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 associated with higher risk of kidney failure and heart failure (adjusted hazard ratio [95% confidence interval] for zero or one versus two copies of : 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 (>0.10). In summary, the loss of was significantly associated with incident kidney and heart failure, independent of traditional risk factors. These results suggest function is a potential treatment target for the prevention of kidney and heart failure.