Objective: To investigate polymorphisms in postinsulin receptor signaling. To investigate PIK3R1, SLC2A4, SLC2A4RG, and MEF2A to determine whether these genes are associated with susceptibility to polycystic ovary syndrome (PCOS) or key phenotypic features of insulin resistance in subjects with PCOS. Design: Case-control study. Setting: Participants with PCOS were recruited from a clinical practice database, and controls from the general community. Patient(s): One hundred seventy-three patients with PCOS conforming to the National Institutes of Health (NIH) diagnostic criteria, all of Caucasian descent; 107 normally ovulating women of white descent from the general community. Intervention(s): Drawing of blood for DNA extraction. Main Outcome Measure(s): Frequency of PIK3R1, SLC2A4, SLC2A4RG, and MEF2A polymorphisms in case and control subjects. Result(s): No significant difference between the frequency of the polymorphisms in case and control women was identified. No single nucleotide polymorphism studied in any of these four genes was associated with the PCOS phenotype. Conclusion(s): Polymorphisms in the PIK3R1, SLC2A4, SLC2A4RG, and MEF2A genes are not associated with key PCOS phenotypes.