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Background: Physical activity and vitamin D receptor (VDR) have been associated with type 2 diabetes mellitus (T2DM). However, the associations of VDR methylation with T2DM and physical activity remained unknown. We aimed to investigate whether VDR methylation was a link between physical activity and T2DM. Methods: A 1:1 matching case‐control study was designed based on the Henan Rural Cohort Study, including 272 pairs of T2DM patients and nonpatients. Physical activity level was assessed using the International Physical Activity Questionnaire. The high‐resolution melt method was applied to determine the methylation level of the promoter region of VDR. The association between physical activity and T2DM was analyzed with a conditional logistic regression model. The effect modification of VDR methylation levels on the association between physical activity and T2DM was conducted. A multivariate correlation analysis model was applied to investigate correlations of VDR methylation with insulin sensitivity. Results: Physical activity level was associated with T2DM risk (crude model: odds ratio [OR] 0.611; 95% CI, 0.416‐0.897; adjusted model: OR 0.619; 95% CI, 0.418‐0.917). In effect modification analysis, the effects of physical activity on T2DM were stronger for low VDR methylation levels than for high (P =.025). Moreover, VDR methylation levels were associated with insulin (r = −0.089, P =.039) as well as homeostatic model assessment of insulin resistance (r = −0.098, P =.022). Conclusions: The methylation status of the VDR promoter is associated with the secretion and sensitivity of insulin. VDR methylation attenuates the association between physical activity and T2DM, indicating that proactively physical activity may reduce the risk of T2DM, especially in people with low VDR methylation level. [ABSTRACT FROM AUTHOR]

Background: Previous studies reported that testosterone and DNA methylation of suppressor of cytokine signaling‐3 (SOCS3) were associated with type 2 diabetes (T2D). Testosterone affects SOCS3 gene expression. Therefore, we aimed to investigate how the SOCS3 methylation mediates the relationship between testosterone and T2D among Chinese rural adults. Methods: A case‐control study comprised 365 T2D patients and 651 controls was conducted. Liquid chromatography‐tandem mass spectrometry and MethylTarget were used to determine the levels of serum testosterone and DNA methylation of SOCS3 gene, respectively. The odds ratio (OR) of testosterone or SOCS3 methylation for T2D was calculated using logistic regression models, and β value of testosterone for SOCS3 methylation was evaluated by linear regression models. Furthermore, through mediation analysis the mediating effect of SOCS3 methylation on the association of testosterone with T2D was estimated. Results: After adjusting for multiple variables, the protective effect of testosterone on T2D was found in men (OR = 0.61, 95% confidence interval [CI]: 0.47‐0.80), and the methylation of Chr17:76356190 or Chr17:76356199 was negatively related to T2D in both men and women. Moreover, testosterone was positively associated with Chr17:76356190 methylation in men and Chr17:76356199 methylation in women (both P <.05). The mediation analysis showed that the Chr17:76356190 methylation partly mediated effect of testosterone on T2D in men was approximately 8.2%. Conclusions: High levels of serum testosterone in men and Chr17:76356190 and Chr17:76356199 (SOCS3) methylation were related to a lower prevalent T2D. In addition, Chr17:76356190 methylation partially mediated the effect of testosterone on T2D in Chinese rural men. [ABSTRACT FROM AUTHOR]

Background Vitamin D and the vitamin D receptor ( VDR) are associated with susceptibility to type 2 diabetes mellitus (T2DM). The purpose of the present study was to screen more single nucleotide polymorphisms (SNPs) of VDR and assess their effects on the risk of T2DM in Han Chinese. Method Four SNPs were genotyped in 1191 individuals (397 cases, 794 controls). Allele frequencies and genotype distributions were analyzed. Effects were investigated by evaluating genotype distribution with regard to phenotypes, insulin resistance, and β-cell function. Haplotype analysis and gene risk score (GRS) were used to evaluate the combined and additive roles of VDR SNPs on T2DM pathogenesis. Results There was a significant association between rs739837 and T2DM in two models and allele frequency distribution. The novel locus rs2239179 differed significantly between cases and controls, especially in males and those aged >55 years, in three models and allele frequency distribution. The TT genotype of rs739837 was associated with higher triglyceride than GG and TG genotypes, and higher total cholesterol levels than the GG genotype. Compared with the GTGA haplotype, the GCGG haplotype reduced the risk of T2DM. Trend Chi-squared tests showed that there was significant association between the weighted GRS and the risk of T2DM ( Ptrend = 0.034). Conclusion This study provides novel evidence that rs739837 is associated with lipid metabolism in T2DM patients. The rs739837 and rs2239179 SNPs were associated with the risk of T2DM in Han Chinese. The VDR SNPs had combined and additive effects on the risk of T2DM. [ABSTRACT FROM AUTHOR]