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

SummaryObjective 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.