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. 2007;64(2):107-13.
doi: 10.1159/000101962. Epub 2007 May 2.

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

Caroline G P Roberts  1 , Haiqing Shen, Braxton D Mitchell, Coleen M Damcott, Alan R Shuldiner, Annabelle Rodriguez
Affiliations

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

Caroline G P Roberts et al. Hum Hered. 2007.

Abstract

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.

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Figures

Fig. 1
Fig. 1
Gene structure and pairwise LD among SNPs in SCARB1. The upper portion of the figure shows the gene structure and location of polymorphisms. The lower portion of the figure shows a schematic pairwise LD, calculated as D′ and r2 among the polymorphic SNPs in the Amish. The lines connect each SNP name and the position with the corresponding cell in the LD matrix. Magnitude and significance of the D′ and r2 is illustrated by shading with a red to white or a blue to white gradient reflecting higher to lower LD values.
Fig. 2
Fig. 2
Adjusted HDL-C levels in men and women according to rs5888 and rs5891 genotype. Mean HDL-C levels for men and women according to rs5888 and rs5891 genotype are shown. The p value for women is statistically significant for trend while the p value for men is not significant. There is a significant gene × gender interaction for rs5888 (p < 0.005).
See this image and copyright information in PMC

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