In order to assess the relationship between previously reported cholesteryl ester transfer protein (CETP) genotypes and phenotypes to lipid levels and coronary risk, Thompson et al. systematically reviewed the literature on specific CETP polymorphisms and outcomes including lipid levels and/or coronary risk. A total of 3 common (TaqIB [rs708272], I405V [rs5882] and -629C>A [rs1800775]) and 3 uncommon (D442G [rs2303790], -631C>A [rs1800776] and R451Q [rs1800777]) CETP polymorphisms were studied. They found 92 studies that assessed the relationship between CETP phenotypes and outcomes, which included more than 147,000 individuals (and more than 27,000 coronary cases). They showed that common CETP genotypes were associated with decreased CETP activity and mass by approximately 5 to 10%. For instance, for each A allele inherited, individuals with the TaqIB polymorphism had lower mean CETP mass [-9.7% (95% CI, -11.7 to -7.8%)] and lower mean CETP activity [-8.6% (95% CI, -13.0% to -4.1%). These polymorphisms were associated with increased plasma levels of HDL cholesterol and apolipoprotein AI levels and a slightly reduced coronary risk. The reduced per-allele coronary risk was found to be of a similar magnitude as the reduced coronary risk tied to the decrease in HDL cholesterol associated with these polymorphisms. The paper was accompanied by an editorial by Peter W. F. Wilson who positioned the study by Thompson et al. in relation to other studies that have investigated the relationship between genetic variants of other mediators of the lipid-lipoprotein metabolism, such as the LDL receptor or apolipoprotein E4. He also highlighted one of the study’s key strengths, mentioning that the scientific presentation of the results “allows a view through a lens that provides greater metabolic depth of the field than usual, and lends insights into the pathophysiology of atherosclerosis that are not usually met with meta-analyses”.
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