Polymorphisms of the HDL receptor gene associated with HDL cholesterol levels in diabetic kindred from three populations

OBJECTIVE: We examined polymorphisms in the HDL receptor, SR-BI, for association with plasma HDL cholesterol levels. METHODS: Study subjects, including 847 women and 725 men, were from families originally ascertained for type 2 diabetes from Finland, Sweden and Israel. Four common polymorphisms were examined in linear regression analysis: an exon 1 missense (EX1), exon 8 silent (EX8), intron 5 (IVS5) and intron 10 (IVS10) variants. RESULTS: Genotype combinations for the three polymorphisms in linkage disequilibrium (IVS5, EX8 and IVS10) were found to be associated with HDL-C among women from the Israeli (p = 0.01) and Swedish (p = 0.06) populations. In Finnish women, the association was only apparent after taking into account effect modification by triglyceride levels (p = 0.04). One specific pattern of genotypes, denoted by presence of the IVS5_T and EX8_C alleles, and absence of the IVS10_G allele, was consistently associated with the lowest mean levels of HDL-C in women from all three populations. These same associations were not found in men. CONCLUSIONS: Polymorphic variation of the SR-BI gene may influence HDL-C levels and act in a sex-dependent manner.