Androgen Receptor Dna Methylation Is An Independent Determinant Of Glucose Metabolic Disorders In Women And Testosterone Plays Moderation Effects

Background We have previously shown that serum testosterone was associated with impaired fasting glucose (IFG) and type 2 diabetes (T2D). Testosterone can be acting through binding the androgen receptor (AR). Therefore, we aimed to explore the independent associations of AR DNA methylation (ARm) with IFG and T2D and the moderation effects of serum testosterone on the associations.Methods A case-control study with 1065 participants including 461 men and 604 women was performed. ARm in peripheral blood sample and serum testosterone were measured using pyrosequeuncing and liquid chromatography-tandem mass, respectively. Multivariable logistic regression was performed to estimate the associations of ARm (including 2 cytosine-phosphoguanine [CpG] islands and average methylation levels) with different glucose status. Serum testosterone was used as a moderator to estimate the moderation effect.Results After multivariate adjustment, CpG 1, 2 and CpG average methylation were all significantly associated with IFG (CpG 1: Odds ratio (OR) = 4.80, 95% confidence interval (CI): 2.24-10.27; CpG 2: OR = 4.35, 95% CI: 2.50-7.58; CpG average: OR = 11.73, 95% CI: 5.36-25.67) in women. In addition, testosterone played negative moderation effects in above associations. Moreover, no significant independent associations of methylation levels with T2D was observed both in men and women.Conclusion Our findings demonstrate that ARm was positively associated with IFG in women and the associations would be weakened by testosterone. The individuals experiencing low testosterone and ARm levels reported a lower state of IFG than those who experienced high levels of testosterone and ARm in women.