Association of type 2 diabetic nephropathy with methylation status of genomic DNA and connective tissue growth factor gene promoter
10.3760/cma.j.issn.1001-7097.2012.03.006
- VernacularTitle:基因组DNA和结缔组织生长因子基因启动子甲基化状态与2型糖尿病肾病的关系
- Author:
Bin YI
;
Xu CAI
;
Hao ZHANG
;
Jianwen WANG
;
Yan LIU
;
Miao YANG
- Publication Type:Journal Article
- Keywords:
Diabetic nephropathy;
Connective tissue growth factor;
DNA;
Methylation
- From:
Chinese Journal of Nephrology
2012;28(3):189-193
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the role of methylation of genomic DNA and connective tissue growth factor (CTGF) gene promoter in the pathogenesis of diabetic nephropathy (DN). Methods According to the WHO 1999 guideline for diabetes mellitus diagnosis and classification standard,90 patients diagnosed as diabetes mellitus and 30 healthy volunteers were enrolled in this study.All the participants were divided into diabetes mellitus without DN (DM) group (n=48),DN group (n=42) and healthy control group (n=30) accordingly.DNA was extracted from the peripheral blood and high pressure liquid chromatography (HPLC) was used to measure the overall methylation level of genomic DNA.The methylation status of CTGF gene promoter was determined by PCR and sequencing analysis.Serum CTGF protein level was measured by ELISA.Results The overall methylation level of genomic DNA was 5.23％±0.09％ for DN group,4.71％ ±0.03％ for DM group,and 4.37％±0.01％ for healthy control group,with no significant differences among three groups (all P＞0.05).The CTGF promoter methylation level in DN group (22.02％± 12.90％) was significantly decreased,compared to DM group (49.18％±8.01％,P=0.019) or healthy control group (72.18％±19.30％,P=0.000).Moreover,the serum CTGF protein level in DN group [(193.44±11.90) mg/L] was significantly increased,compared to DM group [(127.65±10.30) mg/L,P=0.031] and healthy control group [(95.84±5.10) mg/L,P=0.001]. Conclusion In DN patients,CTGF gene promoter methylation level is significantly decreased,but CTGF protein level is higher as compared to non-DN patients,which indicates that CTGF gene promoter demethylation may be involved in the pathogenesis of diabetic nephropathy.
