Exercise modifies gene variant effects on HDL, MI risk
MedWire News: Researchers report that physical exercise modifies the effect of three common gene variants on levels of high-density lipoprotein (HDL) cholesterol and risk for myocardial infarction (MI) in healthy Caucasian women.
Brendan Everett (Brigham and Women's Hospital, Massachusetts, USA) and colleagues show that increases in HDL cholesterol levels related to variants in the hepatic lipase (LIPC) and cholesteryl ester transfer protein (CETP) genes were amplified in active compared with inactive people, while those related to a common lipoprotein lipase (LPL) gene variant were attenuated.
They also say that the risk for MI associated with carriage of the specific LPL single nucleotide polymorphism (SNP) genotype varies by activity level, whereas risk associated with carriage of the CETP SNP allele is linked to MI risk regardless of activity level.
"This differential modification provides a possible biological explanation for the wide variability in HDL cholesterol response to exercise, and for the clinical observation that some individuals do not experience improvements in HDL cholesterol, despite adopting an exercise regimen," comment the researchers in the journal Circulation: Cardiovascular Genetics.
Using data on nearly 23,000 female participants from the Women's Genome Health Study, whose genetic data were available and for whom information on physical activity and HDL cholesterol had been obtained, the researchers identified SNPs at three loci that showed the strongest modifiable effects on HDL cholesterol, according to levels of physical activity (rs10096633 at LPL, rs1800588 at LIPC, and rs1532624 at CETP).
Per minor allele copy, the researchers observed greater increases in HDL cholesterol for the SNPs in LIPC and CETP among active compared with inactive women (2.3 vs 1.7 mg/dl [0.06 vs 0.04 mmol/l] and 3.3 vs 2.7 mg/dl [0.09 vs 0.07 mmol/l] per copy, respectively).
In contrast, for the SNP in LPL there was a smaller per-allele increase in HDL among active than inactive women (1.0 vs 2.1 mg/dl [0.03 vs 0.05 mmol/l] per copy).
Carriage of the minor allele of the LPL variant was related to a 50% reduction in risk for MI among active participants only, while carrying the minor allele of the CETP SNP was associated with a 30% reduction in MI risk, regardless of activity level.
Minor allele carriage of the LIPC SNP did not appear to provide protection against MI.
"The protection from MI afforded by higher plasma levels of HDL cholesterol may depend both on absolute levels and variation in the genetic determinants of those levels," suggest Everett and team.
They conclude: "This raises the possibility that the effects of lifestyle choices on cardiovascular events may vary by genotype."
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By Nikki Withers