['Genetic variation in diabetes-associated genes cumulatively explain little of the overall heritability of this trait. We sought to determine whether polymorphisms of the scavenger receptor class B, member I (SCARB1), an estrogen-regulated chromosome 12q24 positional candidate diabetes gene, were associated with type 2 diabetes or insulin resistance in a sex-specific fashion.', 'We evaluated 34 haplotype-tagged single-nucleotide polymorphisms (SNPs) of SCARB1 for their association with type 2 diabetes and measures of insulin resistance in two populations: a clinic-based sample of 444 Mexican-American women from Proyecto SALSA and a community-based sample of 830 white women from the Rancho Bernardo Study.', 'We identified significant associations between a tagged SNP in intron 9, rs9919713, and fasting glucose in the SALSA population (P = 2.3 x 10(-4)). In the Rancho Bernardo Study, the same SNP also showed significant association with the related traits homeostasis model assessment for insulin resistance (P = 3.0 x 10(-4)), fasting glucose (P = 1.1 x 10(-3)), and type 2 diabetes (P = 9.0 x 10(-3)). In men from the Rancho Bernardo population, the opposite effect was found (genotype by sex interaction in the Rancho Bernardo population P < 10(-3) for insulin resistance).'] Are polymorphisms of the scavenger receptor class B member 1 associated with insulin resistance with evidence of gene by sex interaction?