Association of type 2 diabetic nephropathy with methylation status of genomic DNA and connective tissue growth factor gene promoter
YI Bin*, CAI Xu, ZHANG Hao, WANG Jian-Wen, LIU Yan, YANG Miao.
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*Department of Nephrology, the Third Xiangya Hospital, Central South University, Changsha 410013, ChinaCorresponding author: ZHANG Hao, Email: zhanghaoliaoqing@163.com
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Received
Revised
Published
1900-01-01
1900-01-01
2012-03-15
Issue Date
2012-03-15
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.
YI Bin*;CAI Xu;ZHANG Hao;WANG Jian-Wen;LIU Yan;YANG Miao. .
Association of type 2 diabetic nephropathy with methylation status of genomic DNA and connective tissue growth factor gene promoter [J]. Chinese Journal of Nephrology, 2012, 28(3): 189-193.
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