Modification of the effects of estrogen therapy on HDL cholesterol levels by polymorphisms of the HDL-C receptor, SR-BI: the Rancho Bernardo Study

Previous studies have found polymorphisms of the HDL receptor, SR-BI, to be associated with plasma HDL-C in women, but not men, suggesting a modifying role of estrogen. We examined whether the association between SR-BI genotypes and HDL-C is modified by use of unopposed estrogen in community-dwelling postmenopausal Caucasian women. Methods: Common polymorphisms in Intron5 and Exon8 of the SR-BI gene were evaluated in 689 women from the Rancho Bernardo Study. Multiple linear regression analysis was carried out adjusting for confounders. Results: HDL-C levels did not differ significantly by genotype in the aggregate population. However, significant interaction was found between estrogen use and Exon8 (p = 0.03), Intron5 (p = 0.03) and Intron5/Exon8 diplotypes (p = 0.01). SR-BI genotype was associated with HDL-C levels only among estrogen users (p = 0.05) and explained 5.3% of the variance in HDL-C in this group. Consistent with prior studies, individuals heterozygous at both Intron5 and Exon8 loci had the lowest HDL-C levels. Among women with symptomatic CHD, the interaction between estrogen use and SR-BI genotype became even stronger. Conclusions: The effect that unopposed estrogen use has on HDL-C may depend on a womanʹs SR-BI genotype.