Association of transforming growth factor-beta (TGF-β) T869C (Leu 10Pro) gene polymorphisms with type 2 diabetic nephropathy in Chinese

Association of transforming growth factor-beta (TGF-β) T869C (Leu 10Pro) gene polymorphisms with type 2 diabetic nephropathy in Chinese.

Introduction

Transforming growth factor-β (TGF-β) is known to play a pivotal role in the regulation of extracellular matrix (ECM) accumulation. Since diabetic nephropathy (DMN) is characterized by basement membrane thickening and mesangial expansion, control of ECM deposition is believed to be important in the pathogenesis of the disease. Recently, TGF-β T869C (Leu 10Pro) gene polymorphism has been identified which may be associated with circulating TGF-β levels.

Methods

In order to examine the relationship between TGF-β gene polymorphism with DMN in Chinese, we carried out a case-control study, which recruited 123 Chinese type 2 diabetic patients with an average duration of diabetes for 12 years. A total of 58 patients who developed DMN (micro- or macroalbuminuria, with or without renal impairment) were compared with 65 diabetic patients without DMN despite similar duration of disease (normoalbuminuric and creatinine <120 μmol/L). TGF-β T869C (Leu 10Pro) gene polymorphism was determined by polymerase chain reaction (PCR).

Results

Both groups of patients had similar baseline characteristics, including blood pressure, diabetic control, and duration of diabetes. Distribution of TGF-β T869C (Leu 10Pro) genotype among the whole group is confined to Hardy Weinberg equilibrium. The DMN+ group has higher frequency of TGF-β CC/CT genotypes than the DMN- group [CC, CT, TT = (DMN+) 46, 45, 9 (%) vs. (DMN-) 37, 37, 26 (%), P < 0.05]. C allele frequency is also higher in the DMN+ group than DMN- group (69% vs. 55%, P < 0.05). The adjusted odds ratio for TGF-β CC/CT vs. TT genotype to develop DMN is 3.8 (3.2 to 4.4). Multivariate logistic regression analysis [hypertension, gender, age, duration of diabetes, hemoglobin (HbA_1c), usage of angiotensin-converting enzyme (ACE) inhibitor, and cholesterol level] showed that TGF-β genotype (P = 0.03) is an independent predictor for type 2 DMN. Among patients with DMN, those with TGF-β CC/CT genotypes also had worse renal function and increased risk for macroalbuminuria.

Conclusion

Our results suggest that TGF-β T869C (Leu 10Pro) gene polymorphism is associated with DMN in Chinese.