Causality Link Between HDL Cholesterol, MI Challenged
Carriers of LIPG 396Ser, those with high genetic score, have high HDL but no reduction in MI risk
THURSDAY, May 17 (HealthDay News) -- Genetic mechanisms that are associated with high plasma levels of high-density lipoprotein (HDL) cholesterol do not reduce the risk of myocardial infarction (MI), adding question to causality of link, according to a study published online May 17 in The Lancet.
Benjamin F. Voight, Ph.D., from the University of Pennsylvania in Philadelphia, and colleagues performed two mendelian randomization analyses to investigate whether the association between high plasma levels of HDL cholesterol and the reduced risk of MI is causal. The single nucleotide polymorphism (SNP) in the endothelial lipase gene (LIPG Asn396Ser) was tested in 20 studies, comprising 20,913 cases of MI and 95,407 controls. In addition, a genetic score composed of 14 common SNPs that associate exclusively with HDL was tested in up to 12,482 cases of MI and 41,331 controls.
The researchers found that, compared with noncarriers, LIPG 396Ser allele carriers had higher HDL cholesterol levels. This difference was expected to correlate with a 13 percent reduction in the risk of MI, but 396Ser did not correlate with the risk of MI (odds ratio [OR], 0.99; P = 0.85). A one standard deviation increase in HDL cholesterol correlated with a reduced risk of MI, based on observational epidemiology (OR, 0.62), but an increase of this magnitude in HDL cholesterol due to the genetic score did not correlate with the risk of MI (OR, 0.93; P = 0.63).
"Some genetic mechanisms that raise plasma HDL cholesterol do not seem to lower risk of MI," the authors write. "These data challenge the concept that raising of plasma HDL cholesterol will uniformly translate into reductions in risk of MI."
Several authors disclosed financial ties to the pharmaceutical, biotechnology, and health care industries.