Association between genetic variation in transforming growth factors beta 1 and beta 3 and renal dysfunction in non-diabetic Chinese

Genetic variants of transforming growth factor (TGF) beta 1 have been reported to be associated with diabetic nephropathy. Few studies investigated polymorphisms in the TGF-beta 1 and TGF-beta 3 genes in relation to renal dysfunction in non-diabetic subjects. In all, 601 non-diabetic Chinese were genotyped for the TGF-beta 1 T869C and TGF-beta 3 IVS3-98G > A polymorphisms by PCR-restriction fragment length polymorphism and real-time allele-specific PCR, respectively. Renal dysfunction was defined as a predicted glomerular filtration rate (GFR) of 60mL/min/1.73m(2) or less. 24-hour urinary albumin excretion was measured by an immunonephelometric assay in 352 hypertensive subjects. Our study sample included 184 (30.6%) women, 396 (65.9%) hypertensive patients (65.9%), and 94 (15.6%) patients with renal dysfunction. In men but not women, the TGF-beta 1 TC genotype was significantly (p = 0.0005) overrepresented in patients with renal dysfunction (52.2% vs 36.8% in subjects with normal renal function). Accordingly, in men, with adjustment for age, body mass index, and systolic and diastolic blood pressure, serum creatinine concentration was significantly (p <= 0.03) higher in the TC heterozygotes than TT and CC homozygotes. Furthermore, in 231 male hypertensive patients, with similar adjustments applied, 24-hour urinary albumin excretion was significantly (p = 0.02) higher in the IVS3-98 AA homozygotes than G allele carriers. In further multivariate regression analysis, only in men, TGF-beta 1 and TGF-beta 3 genotypes as independent predictors had statistically significant effect on serum creatinine (p = 0.007) and urinary albumin excretion (p = 0.022), respectively. Our study demonstrated the associations of genetic variants in the TGF-beta genes with renal dysfunction and albuminuria in non-diabetic Han Chinese men but not women.