Genetics
CETP and LPL polymorphisms jointly predict cardiovascular risk in women with high HDL cholesterol and CRP (Atherosclerosis 2011)
Original title: LPL polymorphism (D9N) predicts cardiovascular disease risk directly and through interaction with CETP polymorphism (TaqIB) in women with high HDL cholesterol and CRP
Researchers tested whether women with concurrently high HDL cholesterol and C-reactive protein (CRP), a seemingly paradoxical combination, face increased cardiovascular risk, and whether two reverse-cholesterol-transport genes modify this risk. In this high HDL-C/high-CRP subgroup, the LPL D9N polymorphism directly predicted cardiovascular disease risk (minor allele carriers versus major allele homozygotes: hazard ratio 5.16, 95% CI, 1.43-18.54, p=0.012) and interacted with the CETP TaqIB polymorphism, with the highest risk seen in minor allele carriers of both variants. The authors conclude that in women with high HDL-C and high CRP, the risk association of the LPL polymorphism is compounded by CETP genotype, with the greatest risk in those with presumably decreased activity of both proteins.
Original abstract
Objective: We sought to determine whether concurrently high levels of HDL cholesterol and CRP predict initial cardiovascular events in women, and to assess additional risk involving two genes encoding proteins involved in reverse cholesterol transport.
Methods: A graphical approach identified high-risk subgroups in a population-based female cohort. Polymorphism-associated risk was assessed for CETP (TaqIB [rs708272]) and LPL (D9N [rs1801177]) using multivariable analysis adjusted for clinical parameters and biomarkers.
Results: A high HDL-C/high CRP high-risk subgroup was identified. Multivariable modeling revealed D9N as predicting subgroup cardiovascular disease risk directly (minor allele-carriers versus major allele homozygotes: HR 5.16, 95% CI 1.43-18.54, p = 0.012) and through interaction with TaqIB (highest risk in minor allele carriers of both polymorphisms).
Conclusions: In women with high HDL-C and high CRP levels, an LPL polymorphism associated with risk and interacted with a CETP polymorphism such that the highest risk occurred in subjects with presumably decreased activities of both proteins.
Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 18 August 2026. Methods.