Genetics
CETP TaqIB B2 carriers have higher HDL cholesterol but no lower heart attack risk in a large Physicians Health Study cohort (Atherosclerosis 2002)
Original title: A prospective study of TaqIB polymorphism in the gene coding for cholesteryl ester transfer protein and risk of myocardial infarction in middle-aged men
This prospective nested case-control study examined whether the CETP TaqIB polymorphism, known to associate with higher plasma HDL-cholesterol, is associated with myocardial infarction (MI) risk, in the Physicians Health Study cohort of 14,916 apparently healthy men, comparing 384 participants who developed a first MI to an equal number of age- and smoking-matched controls. The B2B2 genotype, present in 17% of participants, was associated with higher HDL-cholesterol (45 mg/dL for B1B1, 48 for B1B2, 50 for B2B2, P=0.01), but MI risk did not differ significantly across genotypes. After adjustment for coronary risk factors (excluding HDL), relative risks for MI versus B1B1 were 1.12 (95% CI 0.74-1.70) for B1B2 and 0.95 (95% CI 0.54-1.66) for B2B2. In subgroup analysis, B2B2 appeared to have lower MI risk than B1B1 only among individuals with low HDL, while high-HDL participants had lower MI risk regardless of CETP genotype.
Original abstract
Background: Molecular variations in the gene coding for the cholesteryl ester transfer protein (CETP) such as the TaqIB polymorphism are associated with higher plasma high-density lipoprotein (HDL) concentration. However, whether this polymorphism is associated with risk of myocardial infarction (MI) is uncertain.
Methods And Results: In a prospective cohort of 14916 apparently healthy men enrolled in the Physicians' Health Study, allelic status for the TaqIB polymorphism in the CETP gene was determined among 384 participants who subsequently developed a first MI (cases) and among an equal number of age and smoking-matched participants who remained free of cardiovascular disease during follow-up (controls). Overall, the B2B2 genotype was present in 17% of the study participants and was associated with higher HDL cholesterol levels (mean mg/dl [+/- S.D.], 45 +/- 11 for the B1B1 genotype, 48 +/- 13 for the B1B2 genotype and 50 +/- 12 for the B2B2 genotype; P=0.01). However, the risk of developing MI did not differ significantly across these three genotypes. After adjustment for coronary risk factors (but not HDL), the relative risks for future MI were 1.12(95% CI 0.74-1.70) for the B1B2 genotype and 0.95(95% CI 0.54-1.66) for the B2B2 genotype, compared with the B1B1 genotype. In subgroup analysis of individuals with low HDL levels, B2B2 genotype appeared to have a lower risk of MI compared with the B1B1 genotype. However, participants with high HDL were at lower risk of developing MI regardless of their CETP genotype.
Conclusions: In this prospective study of apparently healthy middle-aged US men, carriers of the B2 allele of the TaqIB in the CETP gene had higher HDL concentrations, but did not have lower risk of MI.
Condensed Abstract: In a cohort of apparently healthy middle-aged US men, the relation between CETP genotype and MI risk was prospectively examined in a nested case-control study. After adjusting for coronary risk factors (but not HDL), the 9-year risk of developing MI did not differ significantly by genotype. Comparing to the B1B1 genotype, the relative risks for future MI were 1.12 (95% CI 0.74-1.70) for the B1B2 genotype and 0.95 (95% CI 0.54-1.66) for the B2B2 genotype.
Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 19 August 2026. Methods.