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

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-gamma (IFN-gamma), and interleukin-4 (IL-4) on IgA nephropathy in Japanese patients. Methods: We investigated IFN-gamma 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 < 0.01 and 43% versus 23%; P < 0.059 respectively), but there was no difference between the IgA nephropathy and healthy control groups in frequencies of both 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 < 0.01 and 59% versus 34%; P < 0.05, respectively). We could not confirm an association between IgA nephropathy and polymorphisms of genes involved in the renin-angiotensin system. Conclusion: Our results suggest that IFN-gamma and IL-4 gene polymorphisms could influence disease susceptibility and disease progression in IgA nephropathy in Japanese patients.