Impact of interferon-gamma 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 < 0.05, 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.


CONCLUSIONS
Our results suggest that IFN-gamma 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.
Masutani
Kohsuke
K
Departments of Medicine and Clinical Science and Medicine and Biosystemic Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Miyake
Katsuhisa
K
Nakashima
Hitoshi
H
Hirano
Tadashi
T
Kubo
Michiaki
M
Hirakawa
Makoto
M
Tsuruya
Kazuhiko
K
Fukuda
Kyoichi
K
Kanai
Hidetoshi
H
Otsuka
Takeshi
T
Hirakata
Hideki
H
Iida
Mitsuo
M
D000293:Adolescent; D000328:Adult; D000368:Aged; D000483:Alleles; D003404:Creatinine / Q000097:blood; D016207:Cytokines / Q000235:genetics / Q000502:physiology; D018450:Disease Progression; D005260:Female; D005787:Gene Frequency / Q000235:genetics / Q000502:physiology; D005838:Genotype; D005922:Glomerulonephritis, IGA / Q000097:blood / Q000235:genetics* / Q000276:immunology* / Q000473:pathology; D006801:Humans; D007371:Interferon-gamma / Q000235:genetics* / Q000502:physiology; D015847:Interleukin-4 / Q000235:genetics* / Q000502:physiology; D007564:Japan; D007676:Kidney Failure, Chronic / Q000097:blood / Q000235:genetics; D008297:Male; D018895:Microsatellite Repeats / Q000235:genetics / Q000502:physiology; D008875:Middle Aged; D011110:Polymorphism, Genetic / Q000502:physiology*; D018417:Th1 Cells / Q000378:metabolism; D018418:Th2 Cells / Q000378:metabolism
D016207:Cytokines; D015847:Interleukin-4; D007371:Interferon-gamma; D003404:Creatinine