Association of C-509T and T869C polymorphisms of transforming growth factor-beta(1) gene with susceptibility to and progression of IgA nephropathy

作者：Lim CS; Kim YS; Chae DW; Ahn C; Han JS; Kim S^*; Lee JS; Kim IS

来源：Clinical Nephrology, 2005, 63(2): 61-67.

• genetic polymorphism
• IgA nephropathy
• renal survival
• transforming growth factor-beta(1)

Aims: Transforming growth factor (TGF)-beta(1) is a cytokine with both beneficial anti-inflammatory effects and detrimental profibrotic activity in the pathophysiology and progression of glomerulonephritides. The transcriptional activity of the gene for TGF-beta(1) and the plasma levels of TGF-beta(1) protein are associated with C-509T polymorphism at the promoter region, and with T869C (Leu10Pro) polymorphism at codon 10, of the TGF-beta(1) gene. Methods: Using PCR-RFLP and the amplification refractory mutation system PCR, we investigated the C-509T and T869C polymorphisms, respectively, to elucidate whether allele frequency differences exist between IgA nephropathy (IgAN) patients who were followed up for at least 3 years (n = 108) and a non-nal population (n = 55). We also determined the correlations between the TGF-beta(1) polymorphisms and the progression of IgAN. Results: In C-509T polymorphism, there were significant differences in genotype frequency between IgAN patients and normal controls (CC: CT: TT, 20: 29: 33 vs. 11 : 31 : 13, X-2 = 6.299, p = 0.043). In Kaplan-Meier survival analysis, the patients with TT genotype showed a poorer renal survival than those with CC + CT genotypes (p = 0.042). In T869C polymorphism, there were also significant differences in genotype frequency between IgAN patients and normal controls (TT: TC: CC, 4: 79: 25 vs. 0: 52: 2, X-2 = 12.552, p = 0.002). The initial serum creatinine (Scr) level was higher in the patients with CC genotype than in those with TT + TC genotypes. In Kaplan-Meier survival analysis, the patients with CC genotype showed a poorer renal survival than those with TT + TC genotypes, but not to a statistically significant extent (p = 0.076). In the combined survival analyses, the high TGF-beta(1) producer group showed a poor renal survival rate (p = 0.014). Conclusion: Compared to normal population, the frequencies of geno-types producing high TGF-beta(1) protein were higher in IgAN patients. Moreover, patients with genotypes producing high TGF-beta(1) plasma levels showed a poor renal survival rate.

• 出版日期2005-2