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

Abstract

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.