Vitamin D receptor methylation attenuates the association between physical activity and type 2 diabetes mellitus: A case‐control study

Abstract

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.

Methylation of the Vitamin D Receptor Gene in Human Disorders

“…These results suggest that VDR methylation could attenuate the association between physical activity and T2DM. Moreover, the increased methylation levels of the VDR were also associated with decreased levels of serum insulin, confirming its pivotal role in modulating T2DM phenotype [ 44 ] ( Figure 2 ). All these preliminary data encourage additional research on the role of VDR methylation in the above-mentioned diseases, which is still poorly explored.…”

“…However, these preliminary analyses need to be further explored as they represent the only bibliographic data available to date on the role of VDR methylation in recurrent stone formation. In the context of T2DM, VDR methylation has also been analyzed in association with physical activity in a 1:1 matching case–control study [ 44 ]. The HRM approach was performed to determine the methylation levels of the VDR promoter in a 300 bp region comprissing 27 CpGs, both in 272 T2DM patients and healthy CTRs.…”

Association Between Promoter Methylation of Vitamin D Metabolic Pathway Genes and Tuberculosis and Diabetes Comorbidity in a Chinese Han Population: A Case–Control Study

“…Previous studies also reported that the DNA methylation of CYP24A1, CYP27B1, and VDR showed no significant differences in diabetic patients compared with the health control subjects. 18 , 24 , 25 Cavitation is a severity result of pulmonary tuberculosis, which is related to poor prognosis, treatment relapse, higher infectious rates, and development of drug resistance. 26 Our results demonstrated that the DNA methylation profile of all genes selected in patients with TB-DM was not related to three common abnormal CT features, single cavity, multiple cavities, and air bronchogram sign, referring to the methylation status of the candidate genes in the vitamin D metabolic pathway might not affect the prognosis and relapse of TB-DM.…”

“…Previous study in China has proved that DNA methylation of vitamin D might not be involved in the pathogenesis of DM. 24 , 25 Wang et al in their study demonstrated that methylation levels of key genes in the vitamin D metabolic pathway are related to the risk and prognosis of tuberculosis. 14 Additionally, in the meantime, we are conducting this study, there is a rigorous anti-covid-19 battle going on in China, which disturbs our experimental program.…”

Methylation of the Vitamin D Receptor (VDR) gene in human disorders

“…However, these preliminary analyses need to be further explored as they represent the only bibliographic data available to date on the role of VDR methylation in recurrent stone formation. In the contest of T2DM, VDR methylation has also been analysed in association with physical activity in a 1:1 matching case-control study [41]. HRM approach was performed to determine the methylation levels of VDR promoter in a 300 bp region comprising 27 CpGs, both in 272 T2DM patients and healthy CTRs.…”