Association between β2-adrenoceptor (ADRB2) haplotypes and insulin resistance in PCOS

Abstract

OBJECTIVE: The aim of this study was to explore β2-adrenoceptor (ADRB2) haplotype associations with phenotypes and quantitative traits related to insulin resistance (IR) and the metabolic syndrome (MS) in a polycystic ovary syndrome (PCOS) population. A secondary purpose was to assess the association between ADRB2 haplotype and PCOS. DESIGN: Genetic polymorphism analysis. Cross-sectional case-control association study. SETTING: Medical University Hospital and research laboratory. PATIENTS: One hundred and sixty-five unrelated women with PCOS and 116 unrelated women without PCOS (control sample). MEASUREMENTS: Clinical and biochemical measurements, and ADRB2 genotyping in PCOS patients and control subjects. METHODS: ADRB2 haplotypes (comprising rs1042711, rs1801704, rs1042713 and rs1042714 in that order), genotyping and statistical analysis to evaluate associations with continuous variables and traits related to IR and MS in a PCOS population. Associations between ADRB2 haplotypes and PCOS were also assessed. RESULTS: We observed an age-adjusted association between ADRB2 haplotype CCGG and lower insulin (P = 0·018) and HOMA (P = 0·008) in the PCOS sample. Interestingly, the expected differences in surrogate measures of IR between cases and controls were not significant in CCGG/CCGG carriers. In the case-control study, genotype CCGG/CCGG was associated with a 14% decrease in PCOS risk (P = 0·043), taking into account confounding variables. CONCLUSIONS: Haplotype I (CCGG) has a protective role for IR and MS in PCOS.