Association between genetic variation in transforming growth factors beta1 and beta3 and renal dysfunction in non-diabetic Chinese.
Genetic variants of transforming growth factor (TGF) beta1 have been reported to be associated with diabetic nephropathy. Few studies investigated polymorphisms in the TGF-beta1 and TGF-beta3 genes in relation to renal dysfunction in non-diabetic subjects. In all, 601 non-diabetic Chinese were genotyped for the TGF-beta1 T869C and TGF-beta3 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-beta1 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 < or = 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-beta1 and TGF-beta3 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.
Hu
Bang-Chuan
BC
Department of Hypertension and Centre for Epidemiological Studies and Clinical Trials, Ruijin Hospital, Shanghai Institute of Hypertension, Shanghai Jiao Tong University Medical School, Shanghai, China.
Chu
Shao-Li
SL
Wang
Gu-Liang
GL
Gao
Ping-Jin
PJ
Zhu
Ding-Liang
DL
Wang
Ji-Guang
JG
D000225:Adenine; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000419:Albuminuria / Q000209:etiology / Q000503:physiopathology; D044466:Asian People / Q000235:genetics*; D003404:Creatinine / Q000097:blood; D003596:Cytosine; D005260:Female; D014644:Genetic Variation; D005838:Genotype; D005919:Glomerular Filtration Rate; D006147:Guanine; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D006973:Hypertension / Q000235:genetics / Q000652:urine; D007438:Introns; D007668:Kidney / Q000503:physiopathology*; D007674:Kidney Diseases / Q000235:genetics / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D012150:Polymorphism, Restriction Fragment Length; D012737:Sex Factors; D013941:Thymine; D053773:Transforming Growth Factor beta1 / Q000235:genetics*; D053782:Transforming Growth Factor beta3 / Q000235:genetics*
D053773:Transforming Growth Factor beta1; D053782:Transforming Growth Factor beta3; D006147:Guanine; D003596:Cytosine; D003404:Creatinine; D000225:Adenine; D013941:Thymine