Impact of interferon-γ and interleukin-4 gene polymorphisms on development and progression of IgA nephropathy in Japanese patients

Abstract Background: Cytokines have an important role in the pathogenesis and disease progression of immunoglobulin A (IgA) nephropathy. The aim of this study is to investigate the impact of gene polymorphisms of T helper cell subtype 1 (T H 1)/T H 2 cytokines, interferon-γ (IFN-γ), and interleukin-4 (IL-4) on IgA nephropathy in Japanese patients. Methods: We investigated IFN-γ gene ( IFNG ) and IL-4 gene ( IL4 ) polymorphisms in 96 patients with biopsy-confirmed IgA nephropathy who were followed-up for more than 3 years in our outpatient clinic and 61 healthy controls by polymerase chain reaction and direct sequencing methods. IFNG polymorphism was characterized as a microsatellite of intron 1. Four alleles were identified and designated IFNG 112, 114, 116, and 118, corresponding to 12, 13, 14, and 15 repeats, respectively. A variable number of tandem repeat (VNTR) polymorphisms of IL4 also were studied, and alleles were designated IL4 B1 and B2, corresponding to 2 and 3 repeats, respectively. Results: In patients with IgA nephropathy, IFNG 114 allele and IFNG 114 +/+ genotype frequencies were significantly greater than in the healthy control group (60% versus 45%; P P IL4 VNTR allele and genotype. However, frequencies of IL4 B1 allele and B1/B1 genotype in patients with progressive IgA nephropathy (end-stage renal disease or doubling of serum creatinine level; n=34) were significantly greater than corresponding values in the nonprogression group (n = 62; 79% versus 61%; P P Conclusion: Our results suggest that IFN-γ and IL-4 gene polymorphisms could influence disease susceptibility and disease progression in IgA nephropathy in Japanese patients. Am J Kidney Dis 41:371-379.