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

Kohsuke Masutani, Katsuhisa Miyake, Hitoshi Nakashima, Tadashi Hirano, Michiaki Kubo, Makoto Hirakawa, Kazuhiko Tsuruya, Kyoichi Fukuda, Hidetoshi Kanai, Takeshi Otsuka, Hideki Hirakata, Mitsuo Iida

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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 (TH1)/TH2 cytokines, interferon-γ (IFN-y), 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 < 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. 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.

Original languageEnglish
Pages (from-to)371-379
Number of pages9
JournalAmerican Journal of Kidney Diseases
Volume41
Issue number2
DOIs
Publication statusPublished - 01-02-2003

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IGA Glomerulonephritis
Interleukin-4
Interferons
Genes
Alleles
Minisatellite Repeats
Genotype
Disease Progression
Cytokines
Control Groups
Th1 Cells
Disease Susceptibility
Renin-Angiotensin System
Ambulatory Care Facilities

All Science Journal Classification (ASJC) codes

  • Nephrology

Cite this

Masutani, Kohsuke ; Miyake, Katsuhisa ; Nakashima, Hitoshi ; Hirano, Tadashi ; Kubo, Michiaki ; Hirakawa, Makoto ; Tsuruya, Kazuhiko ; Fukuda, Kyoichi ; Kanai, Hidetoshi ; Otsuka, Takeshi ; Hirakata, Hideki ; Iida, Mitsuo. / Impact of interferon-γ and interleukin-4 gene polymorphisms on development and progression of IgA nephropathy in Japanese patients. In: American Journal of Kidney Diseases. 2003 ; Vol. 41, No. 2. pp. 371-379.
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title = "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 (TH1)/TH2 cytokines, interferon-γ (IFN-y), 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 < 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. 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.",
author = "Kohsuke Masutani and Katsuhisa Miyake and Hitoshi Nakashima and Tadashi Hirano and Michiaki Kubo and Makoto Hirakawa and Kazuhiko Tsuruya and Kyoichi Fukuda and Hidetoshi Kanai and Takeshi Otsuka and Hideki Hirakata and Mitsuo Iida",
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Masutani, K, Miyake, K, Nakashima, H, Hirano, T, Kubo, M, Hirakawa, M, Tsuruya, K, Fukuda, K, Kanai, H, Otsuka, T, Hirakata, H & Iida, M 2003, 'Impact of interferon-γ and interleukin-4 gene polymorphisms on development and progression of IgA nephropathy in Japanese patients', American Journal of Kidney Diseases, vol. 41, no. 2, pp. 371-379. https://doi.org/10.1053/ajkd.2003.50046

Impact of interferon-γ and interleukin-4 gene polymorphisms on development and progression of IgA nephropathy in Japanese patients. / Masutani, Kohsuke; Miyake, Katsuhisa; Nakashima, Hitoshi; Hirano, Tadashi; Kubo, Michiaki; Hirakawa, Makoto; Tsuruya, Kazuhiko; Fukuda, Kyoichi; Kanai, Hidetoshi; Otsuka, Takeshi; Hirakata, Hideki; Iida, Mitsuo.

In: American Journal of Kidney Diseases, Vol. 41, No. 2, 01.02.2003, p. 371-379.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Impact of interferon-γ and interleukin-4 gene polymorphisms on development and progression of IgA nephropathy in Japanese patients

AU - Masutani, Kohsuke

AU - Miyake, Katsuhisa

AU - Nakashima, Hitoshi

AU - Hirano, Tadashi

AU - Kubo, Michiaki

AU - Hirakawa, Makoto

AU - Tsuruya, Kazuhiko

AU - Fukuda, Kyoichi

AU - Kanai, Hidetoshi

AU - Otsuka, Takeshi

AU - Hirakata, Hideki

AU - Iida, Mitsuo

PY - 2003/2/1

Y1 - 2003/2/1

N2 - 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 (TH1)/TH2 cytokines, interferon-γ (IFN-y), 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 < 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. 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.

AB - 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 (TH1)/TH2 cytokines, interferon-γ (IFN-y), 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 < 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. 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.

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