摘要
目的探讨瘦素基因启动子区甲基化及蛋白表达与糖调节受损（impaired glucose regulation，IGR）以及2型糖尿病（type2 diabetes mellitus，T2DM）的相关性。方法采用甲基化特异性PCR对不同血糖水平的个体进行Leptin基因启动子区甲基化检测。用双抗体夹心ABC-酶联免疫吸附法检测血液标本中的瘦素蛋白表达量。结果与正常对照组（59．2％）相比，T2DM和IGR组Leptin基因的甲基化率偏低（分别为31．5％和43．6％），差异具有统计学意义（x2分别为22．499，5．109，P值均〈O．05）。T2DM与IGR组相比甲基化率偏低（x2=3．962，P〈O．05），差异具有统计学意义。患者的瘦素含量相对于正常人均偏高，但仅T2DM组与正常人差异具有统计学意义（q=6．81，P（O．01）。直线回归分析提示，瘦素含量随DNA甲基化程度的降低有增高的趋势，两者呈显著负相关（r=-0．95，P〈O．01）。结论Leptin基因启动子区甲基化与瘦素代谢紊乱可能参与糖尿病的发生和发展。检测IGR和T2DM患者Leptin基因启动子区的甲基化状态和基因蛋白表达，对于早期干预、延缓病程具有一定的参考价值。
Objective To assess the association between leptin gene promoter methylation and serum leptin concentrations in patients with impaired glucose regulation （IGR） and type 2 diabetes mellitus （T2DM）. Methods Methylation status of leptin gene promoter was determined with methylation-specific polymerase chain reaction. Serum l.eptin concentrations were determined using enzyme-linked immunosorbent assay. Results Among three groups of individuals with different levels of glucose, the methylation rates of leptin gene in IGR and T2DM groups were 43.6% and 31. 5%, respectively, which were significantly lower than that of healthy subjects （59. 2%;X2 = 22. 499 and 5. 109, respectively, P〈0. 05）. A lower methylation rate was also observed in T2DM group compared with IGR group （X2 = 3. 962, P〈0. 05）. Leptin levels in both T2DM and IGR groups were elevated compared with normoglycemic subjects, but only T2DM group was significantly higher （q=6.81, P〈0.01）. Linear regression analysis indicated that serum leptin concentrations has increased along with declining of DNA methylation rate （r=- 0.95, P〈 0.01 ）. Conclusion Lower levels of leptin gene promoter DNA methylation and serum leptin concentrations are associated with the development of diabetes. Measurement of the methylation status of leptin gene promoter and expression can facilitate early intervention of the disease.
出处
《中华医学遗传学杂志》
CAS
CSCD
北大核心
2012年第4期474-477,共4页
Chinese Journal of Medical Genetics
基金
武汉市科技计划项目（201161038344）
