Association of transforming growth factor-beta (TGF-beta) T869C (Leu 10Pro) gene polymorphisms with type 2 diabetic nephropathy in Chinese.
BACKGROUND
Transforming growth factor-beta (TGF-beta) 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-beta T869C (Leu 10Pro) gene polymorphism has been identified which may be associated with circulating TGF-beta levels.


METHODS
In order to examine the relationship between TGF-beta 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 micromol/L). TGF-beta 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-beta T869C (Leu 10Pro) genotype among the whole group is confined to Hardy Weinberg equilibrium. The DMN+ group has higher frequency of TGF-beta 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-beta 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 (HbA1c), usage of angiotensin-converting enzyme (ACE) inhibitor, and cholesterol level] showed that TGF-beta genotype (P = 0.03) is an independent predictor for type 2 DMN. Among patients with DMN, those with TGF-beta CC/CT genotypes also had worse renal function and increased risk for macroalbuminuria.


CONCLUSIONS
Our results suggest that TGF-beta T869C (Leu 10Pro) gene polymorphism is associated with DMN in Chinese.
Wong
Teresa Yuk Hwa
TY
Department of Medicine and Therapeutics, The Chinese University of Hong Kong, The Prince of Wales Hospital, Shatin, Hong Kong. wgteresa@alumni.cuhk.net
Poon
Peter
P
Chow
Kai Ming
KM
Szeto
Cheuk Chun
CC
Cheung
Man Kuen
MK
Li
Philip Kam Tao
PK
D000368:Aged; D000369:Aged, 80 and over; D044466:Asian People / Q000235:genetics; D016022:Case-Control Studies; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics*; D003928:Diabetic Nephropathies / Q000208:ethnology / Q000235:genetics*; D003930:Diabetic Retinopathy / Q000208:ethnology / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D017354:Point Mutation; D011110:Polymorphism, Genetic; D011237:Predictive Value of Tests; D012720:Severity of Illness Index; D016212:Transforming Growth Factor beta / Q000235:genetics*
D016212:Transforming Growth Factor beta