Transforming growth factor-beta1 gene polymorphism modifies the histological and clinical manifestations in Japanese patients with IgA nephropathy.
Transforming growth factor (TGF)-beta1, a multifunctional cytokine, which regulates proliferation and differentiation of a variety of cell types, has the central role in the development and progression of renal injury in both animal models and human. Although it has been suggested that genetic variations in the TGF-beta1 gene are associated with the activity of the gene product, their clinical significance in glomerular disease is unknown. We investigated whether the polymorphisms of C-509T and T869C in TGF-beta1 account for interindividual variation in manifestations of IgA nephropathy (IgAN) using 626 Japanese subjects including 329 patients with histologically proven IgAN and 297 healthy controls with normal urinalysis. The frequencies of genotypes, alleles, and major haplotypes were similar between the patients and controls. The C-509T and T869C polymorphisms were in tight linkage disequilibrium, and the major haplotypes were C-C and T-T, which accounted for more than 95% of the total. In patients with -509CC and in those with the 869CC, urinary protein excretion was higher than in those with other genotypes, whereas no difference in other clinical manifestations was noted. Moreover, patients with -509CC and those with 869CC genotypes presented with a significant higher score of mesangial cell proliferation than in those with other genotypes. These results suggest that TGF-beta1 gene polymorphisms are specifically associated with heavy proteinuria and mesangial cell proliferation in Japanese patients with IgAN, although they do not confer susceptibility to this disease.
Sato
F
F
Division of Clinical Nephrology and Rheumatology, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.
Narita
I
I
Goto
S
S
Kondo
D
D
Saito
N
N
Ajiro
J
J
Saga
D
D
Ogawa
A
A
Kadomura
M
M
Akiyama
F
F
Kaneko
Y
Y
Ueno
M
M
Sakatsume
M
M
Gejyo
F
F
D000328:Adult; D000368:Aged; D001483:Base Sequence; D016022:Case-Control Studies; D004247:DNA / Q000235:genetics; D005260:Female; D005787:Gene Frequency; D005922:Glomerulonephritis, IGA / Q000235:genetics* / Q000276:immunology* / Q000473:pathology; D006239:Haplotypes; D006801:Humans; D007564:Japan; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D016212:Transforming Growth Factor beta / Q000235:genetics*; D053773:Transforming Growth Factor beta1
C508960:TGFB1 protein, human; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D004247:DNA