The combination of polymorphisms within interferon‐γ receptor 1 and receptor 2 associated with the risk of systemic lupus erythematosus

Nakashima, Hitoshi; Inoue, Hisako; Akahoshi, Mitsuteru; Tanaka, Yosuke; Yamaoka, Kunihiro; Ogami, Eiichi; Nagano, Sukehisa; Arinobu, Yojiro; Niiro, Hiroaki; Otsuka, Takeshi; Niho, Yoshiyuki

doi:10.1016/s0014-5793(99)00701-2

Cited by 57 publications

(31 citation statements)

References 10 publications

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“…Candidate genes for Sxb-4 are Ifngr1 and Myb; Ifngr1 encodes IFN-␥ receptor 1. The frequency of heterozygous amino acid polymorphism (V14M) of IFNGR1 in human SLE patients is significantly higher than in the control population (56). c-myb expression and aberrant lymphocyte proliferation are associated in MRL/lpr mice (57).…”

Section: Discussionmentioning

confidence: 99%

Genetic Dissection of Vasculitis, Myeloperoxidase-Specific Antineutrophil Cytoplasmic Autoantibody Production, and Related Traits in Spontaneous Crescentic Glomerulonephritis-Forming/Kinjoh Mice

Hamano

Tsukamoto

Abe

et al. 2006

The Journal of Immunology

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The spontaneous crescentic glomerulonephritis-forming/Kinjoh (SCG/Kj) mouse is a model of human crescentic glomerulonephritis and vasculitis associated with the production of the myeloperoxidase (MPO)-specific antineutrophil cytoplasmic autoantibody (MPO-ANCA). Although the disease is mediated initially by mutation of the Fas gene (lpr), SCG/Kj mice also have non-Fas predisposing genetic factors. To define these factors, genome-wide quantitative trait locus (QTL) mapping was performed on female (B6× SCG/Kj) F2 intercross mice. Fourteen non-Fas QTLs were identified. QTLs of glomerulonephritis were located on chromosomes 1, 10, 13, 16, and 17, vasculitis on chromosomes 1 and 17, splenomegaly on chromosome 1, hypergammaglobulinemia on chromosomes 1, 2, 4, 6, 7, 11, 13, and 17, antinuclear Ab on chromosomes 1, 8, 10, and 12, and MPO-ANCA production on chromosomes 1 and 10. Significant QTLs derived from SCG/Kj on chromosomes 1, 2, 7, and 13 were designated Scg-1 to Scg-5, respectively, and those derived from B6 on chromosomes 4, 6, 17, and 10 were designated Sxb-1 to Sxb-4, respectively. Two loci linked to MPO-ANCA production on chromosomes 1 and 10 were designated Man-1 and Man-2 (for MPO-ANCA), respectively. Although both Scg-1 and Scg-2 were on chromosome 1 and shared several functions, it was of interest that aberrant MPO-ANCA production was exclusively controlled by Man-1, the centromeric half region of the Scg-2 chromosomal segment. We also examined the epistatic effects between the lpr mutation and non-Fas susceptibility genes. QTLs are discussed in relation to previously described loci, with emphasis on their candidate genes.

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Section: Discussionmentioning

confidence: 99%

Genetic Dissection of Vasculitis, Myeloperoxidase-Specific Antineutrophil Cytoplasmic Autoantibody Production, and Related Traits in Spontaneous Crescentic Glomerulonephritis-Forming/Kinjoh Mice

Hamano

Tsukamoto

Abe

et al. 2006

The Journal of Immunology

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“…21 Second, the 64Q allele was positively associated with the occurrence of systemic lupus erythematosis, which is considered to be a Th2 disease. 20 And third, in a British population the 64Q allele showed a weak association with low immunoglobulin E levels. 22 Taken together, altered cell surface expression of IFN-gR2 due to the Q64R polymorphism, may influence the strength of IFN-g responses, and by consequence the polarisation of T cells towards Th1 or Th2.…”

Section: Discussionmentioning

confidence: 94%

“…Variations reported in healthy individuals are T58R (population allele frequency 0-18%), Q64R (9-57%), E147 K (0-2%) and K182E (0-4%; National Center for Biotechnology Information, single-nucleotide polymorphism database). Previous studies suggested an association between the Q64R polymorphism and immune-related disease: for instance, the 64Q allele was described as a risk factor for systemic lupus erythematosis, 20 whereas in patients with multiple sclerosis, the 64R allele correlated with a progressive onset of disease. 21 Furthermore, the 64Q allele was weakly associated with low serum immunoglobulin E levels.…”

Section: Introductionmentioning

confidence: 99%

Effect of amino acid substitutions in the human IFN-γR2 on IFN-γ responsiveness

et al. 2011

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Patients with interferon-g receptor (IFN-gR) null mutations have severe infections with poorly pathogenic Mycobacteria. The IFN-gR complex involves two IFN-gR1 and two IFN-gR2 chains, in which several amino acid substitutions, some linked to disease and some apparently naturally occurring, have been described. We developed a model system to study functional effects of genetic variations in IFN-gR2. We retrovirally transduced wild-type IFN-gR2 and IFN-gR2 carrying presently known amino acid substitutions in various human cell lines, and next determined the IFN-gR2 expression pattern as well as IFN-g responsiveness. We determined that the T58R, Q64R, E147K and K182E variants of IFN-gR2 are fully functional, although the Q64R variant may be expressed higher on the cell membrane. The R114C, T168N and G227R variants were identified in patients that had disseminated infections with non-tuberculous Mycobacteria. Of these genetic variants, T168N was confirmed to be completely non-functional, whereas the novel variant G227R, and the previously reported R114C, were partial functional. The impaired IFN-g responsiveness of R114C and G227R is mainly due to reduced receptor function, although expression on the cell membrane is reduced as well. We conclude that the T58R, Q64R, E147K and K182E variants are polymorphisms, whereas the R114C, T168N and G227R constitute mutations associated with disease.

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“…3,[31][32][33][34][35][36][37] In this study, this is the first investigation of the association of IL-18 promoter polymorphisms with The w 2 test (2 Â 2 table) was performed to obtain the P-value. The percentages of SLE and control with ht1 were compared with the percentages of SLE and control without ht1.…”

Section: Discussionmentioning

confidence: 99%

Disease association of the interleukin-18 promoter polymorphisms in Taiwan Chinese systemic lupus erythematosus patients

et al. 2007

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Interleukin (IL)-18, an important mediator of innate and adaptive immunity, plays multiple roles in chronic inflammation, in autoimmune diseases, in a variety of cancers and in number of infectious diseases. IL-18 promoter polymorphisms have been also noted associated with various inflammatory diseases. We investigated the association of IL-18 promoter polymorphisms (À656T/G, À607A/C and À137C/G) with systemic lupus erythematosus (SLE) in Taiwan Chinese patients and controls. Six haplotypes (hts) were identified from the three promoter polymorphisms. The genotype distribution of the ht1 (GCC), ht2 (TAC), ht4 (GAC) and ht5 (TCC) were different in patients and controls (Po0.002). Moreover, the haplotype and genotype frequencies of ht1 were significantly increased in patients with discoid rash (P ¼ 0.045, odds ratio (OR): 2.01, 95% confidence interval (CI): 1.01-4.00; P ¼ 0.027, OR: 5.13, 95% CI: 1.41-18.68). In addition, the homozygous genotype ht1/ht1 was significant increased in patients with serositis (P ¼ 0.015, OR: 9.78, 95% CI: 1.55-61.73). These observations suggest that the three promoter polymorphisms contribute to the genetic background of SLE pathogenesis.

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The combination of polymorphisms within interferon‐γ receptor 1 and receptor 2 associated with the risk of systemic lupus erythematosus

Cited by 57 publications

References 10 publications

Genetic Dissection of Vasculitis, Myeloperoxidase-Specific Antineutrophil Cytoplasmic Autoantibody Production, and Related Traits in Spontaneous Crescentic Glomerulonephritis-Forming/Kinjoh Mice

Genetic Dissection of Vasculitis, Myeloperoxidase-Specific Antineutrophil Cytoplasmic Autoantibody Production, and Related Traits in Spontaneous Crescentic Glomerulonephritis-Forming/Kinjoh Mice

Effect of amino acid substitutions in the human IFN-γR2 on IFN-γ responsiveness

Disease association of the interleukin-18 promoter polymorphisms in Taiwan Chinese systemic lupus erythematosus patients

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