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November 5, 2008

ABCA1 Gene Mutations, HDL Cholesterol Levels, and Risk of Ischemic Heart Disease—Reply

JAMA. 2008;300(17):1997-1998. doi:10.1001/jama.2008.540

In Reply: The overall objective of our study was to examine whether a lifelong lowering of HDL cholesterol levels, without corresponding higher levels of plasma triglycerides or atherogenic remnant lipoproteins,1 was associated with increased risk of IHD. To test this hypothesis, we used heterozygotes for mutations in ABCA1 associated with low cellular cholesterol efflux, as well as with substantial, lifelong lowering of HDL levels, and showed no increase in risk. These results question the hypothesis of reverse cholesterol transport, an active research field. We agree with Dr Brunham and colleagues that genetic variants in ABCA1 may have effects on atherosclerosis independent of effects on HDL levels.2-4 However, there are some inaccuracies in their letter.