Variants in scavenger receptor class B type I gene are associated with HDL cholesterol levels in younger women

Objective: Variants within the scavenger receptor class B type I (SCARB1) receptor gene have been previously associated with lipid levels, especially in women, with some studies reporting the association to be stronger in the presence of diabetes or post-menopausal estrogen use. Based on the reported gender-specific association and modification effect of estrogen on lipid levels according to SCARB1 variants, we explored the relationship between SCARBI single nucleotide polymorphisms ( SNPs) and lipid levels in an Amish population to assess sex and age differences. Methods: Eight SCARB1 SNPs, identified from public databases, were genotyped in 919 subjects. Results: Rs5888 and rs3782287 were in high linkage disequilibrium (LD), with r(2) > 0.8. None of the SNPs were significantly associated with lipid levels in men; however in women, rs5888 (p = 0.04) and rs5891 (p < 0.001) were significantly associated with higher HDL-C levels. Rs5891 had an allele frequency of 3% and predicts a missense mutation (Ile135Val), which may be functional. Moreover, rs3782287 (p = 0.023) and rs5888 (p = 0.003) were significantly associated with higher HDL-C levels in women younger than 50 years but not in women aged 50 years or older ( p for interaction between age and rs5888 = 0.045). None of the SNP effects on HDL-C were modified in the presence of diabetes, in either men or women. Conclusions: SCARB1 SNPs influence HDL-C levels in women, particularly in those less than 50 years old. Condensed Abstract: We assessed associations between SCARB1 SNPs and lipid traits in 919 Amish men and women. Two SNPs, rs3782287 and rs5888, were significantly associated with higher HDL-C levels in women younger than 50 years but not in women aged 50 years or older, supporting an interaction between common sequence variants in SCARB1 and estrogen on HDL-C. Copyright (c) 2007 S. Karger AG, Basel