PPARA genetic variants increase the risk for cardiac pumping function reductions following acute high‐altitude exposure: A self‐controlled study

BACKGROUND: Left cardiac pumping function determines the compensatory capacity of the cardiovascular system following acute high‐altitude exposure. Variations in cardiac output (CO) at high altitude are inconsistent between individuals, and genetic susceptibility may play a crucial role. We sought to identify genetic causes of cardiac pumping function variations and describe the genotype–phenotype correlations. METHODS: A total of 151 young male volunteers were recruited and transferred to Lhasa (3,700 m) from Chengdu (<500 m) by plane. Genetic information related to hypoxic signaling and cardiovascular‐related pathways was collected before departure. Echocardiography was performed both before departure and 24 hr after arrival at high altitude. RESULTS: Here we reported that PPARA variants were closely related to high‐altitude cardiac function. The variants of rs6520015 C‐allele and rs7292407 A‐allele significantly increased the risk for cardiac pumping function reductions following acute high‐altitude exposure. In addition, the individuals carrying haplotypes in PPARA, namely, rs135538 C‐allele, rs4253623 A‐allele, rs6520015 C‐allele and rs7292407 A‐allele (C‐A‐C‐A), suffered a 7.27‐fold risk for cardiac pumping function reduction (95% CI: 2.39–22.15, p = .0006) compared with those carrying the wild‐type haplotype. CONCLUSIONS: This self‐controlled study revealed that PPARA variations significantly increased the risk for cardiac pumping function reductions following acute high‐altitude exposure, providing a potential predictive marker before high‐altitude exposure and targets in mechanistic studies.