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LIPG 396Ser allele raised HDL, did not lower risk for MI
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New genetic research fails to support a causal association between higher concentrations of HDL and lower risk for MI.
Using mendelian randomization analyses, researchers compared MI risk in those with an inherited increase in HDL — carriers of the LIPG 396Ser allele. The overall analysis included 20,913 cases of MI and 95,407 controls from 20 studies.
HDL concentrations were higher (mean, 0.14 mmol/L) among carriers of the LIPG 396Ser allele (2.6% frequency) vs. noncarriers, but both groups had similar levels of other lipid and nonlipid risk factors for MI, according to the abstract. Data reveal that the difference in HDL concentrations between carriers and noncarriers is expected to decrease MI risk by 13% (OR=0.87; 95% CI, 0.84-0.91). However, carriers of the allele did not have an increased risk for MI (OR=0.99; 95% CI, 0.88-1.11).
The researchers then constructed a genetic risk score testing for 14 common genetic variants exclusively associated with HDL in nearly 12,500 patients with a history of MI and more than 41,000 controls, according to a press release. A 1 standard deviation (SD) increase in HDL was associated with reduced MI risk (OR=0.62; 95% CI, 0.58-0.66). However, a 1 SD increase due to genetic score was not associated with increased risk (OR=0.93; 95% CI, 0.68-1.26). For LDL, a 1 SD increase in LDL was associated with MI (OR=1.54; 95% CI, 1.45-1.63), which was concordant with that from a genetic score (OR=2.13; 95% CI, 1.69-2.69), the researchers said.
“Some genetic mechanisms that raise plasma HDL cholesterol do not seem to lower risk of MI,” they concluded.
They said these findings challenge the concept that raising HDL will translate into reductions in MI risk.In an accompanying editorial, Seamus C. Harrison, MD, Michael V. Holmes, MD, and Steve E. Humphries, MD, all from the University College London, wrote, “This report adds to a growing number of mendelian randomization analyses investigating biomarkers of CHD.”
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Disclosure: The researchers report being employees of or owning stock in deCODE Genetics and GlaxoSmithline; holding position on the advisory board for AstraZeneca, Merck and Servier; and receiving support from Alnylam Pharmaceuticals, Boehringer Ingelheim, Novartis , Pfizer and Shire Therapeutics. Drs. Harrison, Holmes and Humphries report no relevant financial disclosures.