LPL polymorphism (D9N) predicts cardiovascular disease risk directly and through interaction with CETP polymorphism (TaqIB) in women with high HDL cholesterol and CRP.

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.