Abstract 2182: Physical Activity Modifies the Effect of CETP Polymorphism on HDL-C Levels in 21,705 Women of European Ancestry
Background: Regular physical activity is known to increase high density lipoprotein cholesterol (HDL-C) levels and reduce cardiovascular risk. Whether physical activity (PA) alters the effect of recently discovered genetic determinants of HDL-C has not been well studied.
Methods: Leisure time PA, genome-wide genotype data, and HDL-C levels were obtained on 21,723 middle-aged women of European ancestry enrolled in the Women’s Genome Health Study. We selected 50 single nucleotide polymorphisms (SNPs) at 9 loci that demonstrated genome-wide association with HDL-C levels (all P<1.6X10−7). We tested for modification of the effect of SNPs on HDL-C level by PA, estimated in terms of metabolic equivalent (MET)-hrs/wk.
Results: As anticipated, mean (SD) HDL-C levels were higher for women with PA levels above the median of 8.8 MET-hrs/wk compared to those with PA levels below the median [55.5 (15.4) vs. 52.1 (14.6) mg/dl, respectively; p<0.0001]. We found evidence that the effect of a SNP at the CETP locus (rs708272) on HDL-C levels was modified by PA (Table⇓). Specifically, the increase in HDL-C levels per copy of the minor allele of rs708272 was 3.4 mg/dl in women with PA levels above the median, compared with 2.7 mg/dl in women below the median (p-interaction=0.0096). Effect estimates were similar when analyzing more extreme levels of physical activity. Additional statistically significant interactions between genetic variants and PA were observed at the LPL and LIPC loci (Table⇓).
Conclusions: Physical activity modifies of the effect of genetic determinants of HDL-C levels at the CETP, LPL and LIPC loci.