TRIB1 and GCKR polymorphisms, lipid levels, and risk of ischemic heart disease in the general population.

OBJECTIVE: The goal of this study was to test whether TRIB1-rs2954029 and GCKR-rs1260326 associate with lipid levels and risk of ischemic heart disease (IHD) and myocardial infarction (MI) in the general population. METHODS AND RESULTS: We genotyped >71 000 individuals. Lipid levels were studied cross-sectionally. Risk of IHD and MI was examined prospectively, cross-sectionally, and in a case-control study, and a metaanalysis was performed. TRIB1 TA (50%) and AA (27%) versus TT (23%) genotypes were associated with increased levels of triglycerides (total increase, +0.16 mmol/L; trend, P<0.001), remnant cholesterol (+0.07 mmol/L; P<0.001), apolipoprotein B (+5.7 mg/dL; P<0.001), and low-density lipoprotein cholesterol (+0.11 mmol/L; P<0.001) and with decreased levels of high-density lipoprotein cholesterol (-0.04 mmol/L; P<0.001). In metaanalyses of the 3 studies combined, TRIB1 TA and AA versus TT genotypes were associated with 13% (95% CI, 5% to 20%) and 15% (7% to 23%) increased risk of IHD, and 11% (1% to 21%) and 17% (6% to 30%) increased risk of MI, respectively. Although GCKR CT (46%) and TT (14%) versus CC (40%) genotypes had effects on triglycerides (+0.17 mmol/L; trend, P<0.001), remnant cholesterol (+0.07 mmol/L; P<0.001), and apolipoprotein B (+4.6 mg/dL; P<0.001) similar to those of TRIB1, GCKR did not influence low-density lipoprotein cholesterol levels or risk of IHD or MI. Risks of IHD were similar after stratification for gender, age, body mass index, hypertension, diabetes mellitus, smoking, statin use, alcohol intake, and physical activity. CONCLUSIONS: In the general population, both TRIB1-rs2954029 and GCKR-rs1260326 were associated with lipid levels, whereas TRIB1 was also associated with increased risk of IHD and MI.