To study the role of genetic variation in the 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase (HMGCR) gene in polycystic ovary syndrome (PCOS).Women with and without PCOS were genotyped for seven single-nucleotide polymorphisms (SNPs) in HMGCR. The SNPs and haplotypes were determined and tested for association with PCOS and its component traits.Subjects were recruited from the reproductive endocrinology clinic at the University of Alabama at Birmingham; control subjects were recruited from the surrounding community. Genotyping took place at Cedars-Sinai Medical Center in Los Angeles.A total of 287 white PCOS women and 187 control subjects were studied.Phenotypic and genotypic assessment.HMGCR genotype, PCOS diagnosis, androgen levels, metabolic traits.No association with PCOS was observed. SNP rs4629571 was associated with increased insulin resistance. Haplotype 3 was associated with increased insulin resistance. Haplotype 5 was associated with higher SHBG and lower free T.Variation in the HMGCR gene may influence component features of PCOS, including insulin resistance, SHBG, and free T. HMGCR may thus act as a modifier gene in PCOS.