BACKGROUND: 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 woman's SR-BI genotype.
BACKGROUND: 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 woman's SR-BI genotype.
Authors: Adam C Naj; Michael West; Stephen S Rich; Wendy Post; W H Linda Kao; Bruce A Wasserman; David M Herrington; Annabelle Rodriguez Journal: Circ Cardiovasc Genet Date: 2009-12-11
Authors: Caroline G P Roberts; Haiqing Shen; Braxton D Mitchell; Coleen M Damcott; Alan R Shuldiner; Annabelle Rodriguez Journal: Hum Hered Date: 2007-05-02 Impact factor: 0.444
Authors: Jason Constantineau; Erin Greason; Michael West; Megan Filbin; Jeffrey S Kieft; Martha Z Carletti; Lane K Christenson; Annabelle Rodriguez Journal: Atherosclerosis Date: 2009-11-26 Impact factor: 5.162