Elevation of PTPN1 promoter methylation is a significant risk factor of type 2 diabetes in the Chinese population

Abstract

The present study aimed to investigate the contribution of DNA methylation of the protein tyrosine phosphatase, non-receptor type 1 (PTPN1) gene to the susceptibility to type 2 diabetes (T2D). Peripheral blood mononuclear cells (PBMCs) were collected from 97 patients with T2D and 97 age- and gender-matched controls. DNA methylation of the PTPN1 gene promoter was evaluated by bisulfite pyrosequencing. Independent sample t-tests were used to compare the differences in the PTPN1 promoter and other phenotypes between the patients with T2D and the controls. The results indicated a significant correlation between PTPN1 promoter methylation and the risk of T2D. Additionally, a breakdown analysis by gender revealed that PTPN1 methylation was associated with an increased risk of T2D in females. Furthermore, low-density lipoprotein (r=−0.183, P=0.046) and total cholesterol (r=−0.310, P=0.001) were inversely associated with PTPN1 methylation in females. In conclusion, the results indicate that elevated PTPN1 promoter methylation is a risk factor for T2D in the female Chinese population.

Blood-Based DNA Methylation Biomarkers for Type 2 Diabetes: Potential for Clinical Applications

“…More recently, Huang et al investigated the methylation status of another key regulator of the insulin signaling pathway, PTPN1 , in relation to T2D susceptibility (50). PTPN1 encodes the protein-tyrosine phosphatase 1B protein, which attenuates the insulin signaling pathway by decreasing the phosphorylation of the insulin receptor and/or insulin receptor substrate 1 (68).…”

Sexually dimorphic DNA-methylation in cardiometabolic health: A systematic review

“…In three candidate gene-studies PTPN1 [32], PLA2G7 [26] and BCL11A [27] DNAm was positively associated with serum lipids in women, but not in men. Another study reported that methylation at ABCG1 was negatively associated with triglycerides in women only [28], whereas methylation at LIPC was negatively associated with triglycerides only in men [27].…”

“…Global DNA methylation is a frequent used marker for epigenetic screening since it captures the DNA methylation also at unknown genetic locations while the results of average DNA methylation correlate with the methylation of some trait-relevant genes [23,24]. Ten articles [14,[25][26][27][28][29][30][31][32][33] investigated sex-specific associations between DNAm and blood lipid concentrations applying global n = 2, epi-genome wide n = 1 and candidate gene n = 7 approaches. In total 2,443 non-overlapping participants 1,174 women and 1,269 men from USA, Canada, Finland, UK and China were included in these studies.…”

“…Eight articles [12,27,32,33,[44][45][46][47] reported sex-specific associations between DNAm and glycemic traits and T2D. Five studies were candidate gene studies and three were epi-genome wide studies.…”

The role of DNA methylation in the pathogenesis of type 2 diabetes mellitus

“…Research into the association between T2DM susceptibility and the DNA methylation status of the PTPN1 gene found a significant correlation between the risk for T2DM and the hypermethylation of the eight CpGs in the PTPN1 promoter. A further breakdown analysis by gender showed that this correlation was female specific, as no significant differences were observed between T2DM males and control males in terms of PTPN1 methylation [ 33 ].…”