Modification of the effects of estrogen therapy on HDL cholesterol levels by polymorphisms of the HDL-C receptor, SR-BI: the Rancho Bernardo Study.
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.
Richard
Erin
E
School of Public Health, San Diego State University, 5500 Campanile Dr., San Diego, CA 92182-4162, USA.
von Muhlen
Denise
D
Barrett-Connor
Elizabeth
E
Alcaraz
John
J
Davis
Roger
R
McCarthy
Jeanette J
JJ
D000368:Aged; D018955:CD36 Antigens; D008076:Cholesterol, HDL / Q000097:blood* / Q000378:metabolism*; D015331:Cohort Studies; D015914:Estrogen Replacement Therapy; D005091:Exons; D005260:Female; D005838:Genotype; D006801:Humans; D008875:Middle Aged; D011110:Polymorphism, Genetic; D017698:Postmenopause; D011971:Receptors, Immunologic / Q000235:genetics*; D051116:Receptors, Scavenger; D012737:Sex Factors
D018955:CD36 Antigens; D008076:Cholesterol, HDL; D011971:Receptors, Immunologic; D051116:Receptors, Scavenger