Abstract 168: TMEM8A 1080A>G Polymorphism in a 3’UTR MicroRNA Target Site Influences Aerobic Capacity in Health Individuals: the HUNT Study
Large-scale epidemiological studies demonstrate that aerobic fitness, measured as maximal oxygen uptake (VO2max), is the single best predictor for cardiovascular mortality in both healthy individuals and patients with cardiovascular disease. However, the genetic basis for aerobic capacity has remained unknown. A genome-wide associative study was conducted in 1500 healthy men from the Nord-Trøndelag Health (HUNT3) study in order to identify SNPs located at microRNA target sites associated to VO2max. VO2max was directly measured using a treadmill ramp protocol. The following bioinformatics approach were adopted: first, 2,393,543 conserved microRNA binding sites were initially selected from the TargetScan database out of 25,847,058 already identified in the human genome; second, among 60,480,978 SNPs described in the dbSNP, 388,110 SNPs are located in 3’UTRs and only 0.26% (1000 SNPs) were represented in the Illumina Human Cardio-Metabo (200k) chip. We identified a significant (p=0.003142) SNP (rs540, MAF=0.4131), located in the 3’UTR of the transmembrane protein 8A (TMEM8A) gene, associated with VO2max. TMEM8A is a five membrane-spanning domain, non-globin gene entrapped in the globin pathway. Accordingly, two microRNAs (hsa-miR-190 and hsa-miR-190b) can potentially bind the original variant of the TMEM8A 3’UTR. Interestingly, in the polymorphic variant (G(1080)) these microRNAs are not predicted anymore, and, curiously, five other microRNAs can now bind it (hsa-let-7a-3p, hsa-let-7f-2-3p, hsa-let-7b-3p, hsa-miR-300 and hsa-miR-381). Our data shows for the first time a SNP that can potentially influence microRNA gene expression regulation associated to aerobic capacity in a large population study.
- © 2013 by American Heart Association, Inc.