Effects Of Methylation Of MCP-1, TNF-α And APN On MRNA Expression In Abdominal Adipose Tissue And Its Correlation With Xinjiang Uygur T2DM

Objective: To investigate the relativity between the expression and promoter methylation ofAbdominal adipose tissue’s TNF-α, APN, MCP-1and the obesity and T2DM onset anddevelopment of Xinjiang Uighur.Method: The Abdominal adipose tissue of Uighur are collected and divided into controlgroup (n=50), obesity group（n=48）and T2DM group(n=26). The levels of abdominaladipose tissue’s cytokines (TNF-α, APN, MCP-1) are detected by RT-PCR and the levels ofDNA methylation are detected by DHPLC.Result: the body weight, the waist circumference, hip circumference, waist-hip ratio and thebody mass index of obesity and T2DM groups are significantly higher than those of controlgroup, and the difference is statistically significant (P<0.01). The FPG of diabetes group issignificantly higher than control group and obesity group, and the difference is statisticallysignificant (P<0.01). The TG of obesity group is significantly higher than control group anddiabetes group, and the difference is statistically significant (P<0.01).The TC of obesity groupis significantly higher than control group, and the difference is statistically significant(P<0.01). The HDL of control group is significantly higher than diabetes group and obesitygroup, and the difference is statistically significant (P<0.01).After comparing the cytokine mRNA relative copy number of adipose tissue of each group, itshows that the relative copy number of APN of control group is significantly higher thandiabetes group and obesity group; the relative copy number of TNF-α，MCP-1of controlgroup is significantly lower than diabetes group and obesity group, and the difference isstatistically significant (P<0.05)After carry out multiple linear regression analysis of the sample abdominal adipose tissuecytokine mRNA relative copy number with clinical data, it shows that the expression ofabdominal fat tissue’s APN is significantly negatively correlated with those of BMI, DBP,FPG, TG, LDL and TNF-α, MCP-1(P <0.05), while TNF-α is significantly positive correlatedwith BMI, FPG, TG (P <0.05), and MCP-1is significantly positive correlated with bodyweight, BMI, waist circumference(P <0.05).The methylation of promoter of APN、TNF-α and MCP-1is detected by HPLC. Afterstatistical analysis, it shows that the methylation positive rate of APN of control, obesity anddiabetes group is in turn increased and the difference is statistically significant(34%,47.9%,65.4%, P<0.05). The methylation positive rate of APN of control, obesity and diabetes groupis in turn decreased and the difference is statistically significant (70%,47.9%,26.9%, P<0.01). MCP-1methylation rate is no significant difference among the three groups(0,2.08%,0, P﹥0.05).According to the level of DNA methylation, the samples are divided into methylation positive group and methylation negative group. After comparing the relative mRNA copy number oftwo groups, we find that the level of APN and TNF-α of methylation positive group is higherthan methylation negative group, and the difference is statistically significant (Median:0.2700vs0.7870;0.0542vs0.1988, P<0.01).Conclusion: Conclusion:Abdominal fat tissue cell APN and its TNF-α gene promotermethylation difference caused the difference in mRNA expression level, which is likely to becorrelated to the occurrance and development of T2DM of Xinjiang Uygur people.