The TGF-β gene participates in the development of chronic kidney disease. We investigated whether the 869 T > C, 915 G > C and -800 G > A polymorphisms of TGF-β1 are associated with diabetic nephropathy (DN). Polymorphisms were genotyped in 439 type 2 diabetes mellitus patients, 233 with diabetic nephropathy (DN+) and 206 without (DN-). The sample was characterized for relevant clinical and biochemical parameters. The 869 T > C (P = 0.016; odds ratio (OR) = 1.818, 95% confidence interval (CI) = 1.128-2.930) and the 915 G > C polymorphisms (P = 0.008, OR = 4.073, 95% CI = 1.355-12.249) were associated with diabetic nephropathy. The 869 T > C variant was associated with total cholesterol levels: CC + CT genotypes had a mean cholesterol concentration of 5.62 ± 1.40 mmol/L vs a mean concentration of 5.15 ± 1.40 mmol/L for the TT genotype (P = 0.011). Triglycerides were also higher in CC + CT genotypes (2.49 ± 1.56 mmol/L) in comparison with TT homozygotes (2.1 ± 1.22 mmol/L, P = 0.042). Multivariate logistic regression showed that the polymorphisms 869 T > C and 915 G > C were independent predictors for DN (P = 0.049 and 0.046, respectively). The 869 T > C and 915 G > C polymorphisms within the TGF-β1 gene were associated with DN+. Lower cholesterol and triglycerides levels were observed in TT homozygotes for the 869 T > C polymorphism. The TGF-β1 869 T allele seems to confer protection against DN+. © 2010 The Authors. Nephrology © 2010 Asian Pacific Society of Nephrology.