Transforming growth factor-beta1 gene polymorphism modifies the histological and clinical manifestations in Japanese patients with IgA nephropathy.
Transforming growth factor-beta1 gene polymorphism modifies the histological and clinical manifestations in Japanese patients with IgA nephropathy.
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DOI：
10.1111/j.1399-0039.2004.00256.x
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发表时间：
2004-07
期刊：
影响因子：
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通讯作者：
F. Sato;I. Narita;S. Goto;D. Kondo;N. Saito;J. Ajiro;D. Saga;Asa Ogawa;M. Kadomura;F. Akiyama;Y. Kaneko;M. Ueno;M. Sakatsume;F. Gejyo
中科院分区：
文献类型：
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作者：
F. Sato;I. Narita;S. Goto;D. Kondo;N. Saito;J. Ajiro;D. Saga;Asa Ogawa;M. Kadomura;F. Akiyama;Y. Kaneko;M. Ueno;M. Sakatsume;F. Gejyo
转化生长因子（Transforming growth factor，TGF）-β 1是一种多功能细胞因子，调节多种细胞的增殖和分化，在动物模型和人类肾损伤的发生和发展中起着重要作用。虽然已经表明TGF-β 1基因的遗传变异与基因产物的活性相关，但其在肾小球疾病中的临床意义尚不清楚。我们研究了TGF-β 1的C-509 T和T869 C多态性是否解释了伊加肾病（IgAN）表现的个体间差异，研究对象为626名日本受试者，包括329名组织学证实的IgAN患者和297名尿分析正常的健康对照者。基因型、等位基因和主要单倍型的频率在患者和对照组之间相似。C-509 T和T869 C多态性处于紧密连锁不平衡状态，主要单倍型为C-C和T-T，占总单倍型的95%以上。在-509CC和869 CC患者中，尿蛋白排泄量高于其他基因型患者，而其他临床表现无差异。此外，-509 CC和869 CC基因型患者的系膜细胞增殖评分显著高于其他基因型患者。这些结果表明，TGF-β 1基因多态性与日本IgAN患者的重蛋白尿和系膜细胞增殖特别相关，尽管它们并不赋予这种疾病的易感性。
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.