We are analyzing https://link.springer.com/article/10.1186/ar2516.

Title:
Role of STAT4 polymorphisms in systemic lupus erythematosus in a Japanese population: a case-control association study of the STAT1-STAT4region | Arthritis Research & Therapy
Description:
Introduction Recent studies identified STAT4 (signal transducers and activators of transcription-4) as a susceptibility gene for systemic lupus erythematosus (SLE). STAT1 is encoded adjacently to STAT4 on 2q32.2-q32.3, upregulated in peripheral blood mononuclear cells from SLE patients, and functionally relevant to SLE. This study was conducted to test whether STAT4 is associated with SLE in a Japanese population also, to identify the risk haplotype, and to examine the potential genetic contribution of STAT1. To accomplish these aims, we carried out a comprehensive association analysis of 52 tag single nucleotide polymorphisms (SNPs) encompassing the STAT1-STAT4 region. Methods In the first screening, 52 tag SNPs were selected based on HapMap Phase II JPT (Japanese in Tokyo, Japan) data, and case-control association analysis was carried out on 105 Japanese female patients with SLE and 102 female controls. For associated SNPs, additional cases and controls were genotyped and association was analyzed using 308 SLE patients and 306 controls. Estimation of haplotype frequencies and an association study using the permutation test were performed with Haploview version 4.0 software. Population attributable risk percentage was estimated to compare the epidemiological significance of the risk genotype among populations. Results In the first screening, rs7574865, rs11889341, and rs10168266 in STAT4 were most significantly associated (P < 0.01). Significant association was not observed for STAT1. Subsequent association studies of the three SNPs using 308 SLE patients and 306 controls confirmed a strong association of the rs7574865T allele (SLE patients: 46.3%, controls: 33.5%, P = 4.9 × 10-6, odds ratio 1.71) as well as TTT haplotype (rs10168266/rs11889341/rs7574865) (P = 1.5 × 10-6). The association was stronger in subgroups of SLE with nephritis and anti-double-stranded DNA antibodies. Population attributable risk percentage was estimated to be higher in the Japanese population (40.2%) than in Americans of European descent (19.5%). Conclusions The same STAT4 risk allele is associated with SLE in Caucasian and Japanese populations. Evidence for a role of STAT1 in genetic susceptibility to SLE was not detected. The contribution of STAT4 for the genetic background of SLE may be greater in the Japanese population than in Americans of European descent.
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stat, sle, association, article, lupus, pubmed, japanese, google, scholar, systemic, patients, erythematosus, population, snps, cas, risk, controls, study, analysis, table, genotype, nephritis, data, role, polymorphisms, cells, haplotype, region, japan, healthy, arthritis, rst, allele, gene, genetic, tag, reported, type, snp, behrens, single, statstat, screening, production, antidsdna, ifnγ, university, central, shown, research,

Topics {✒️}

anti-double-stranded dna antibodies anti-double-stranded dna article download pdf traf1/c5 variants influence systemic lupus erythematosus systemic lupus erythematosus cytokine-mediated biological responses genome-wide association scan anti-dsdna antibodies compared complex human diseases full size image research ethics committees case-control association analysis related subjects primary sjögren syndrome case-control association study anti-dsdna antibodies anti-dsdna antibody privacy choices/manage cookies rheumatology revised criteria full access il-23-induced il-17 production baechler ec single nucleotide polymorphisms article number r113 article kawasaki abbreviations anti-dsdna logistic regression analysis interferon regulatory factor-5 anti-dsdna production single causative snp recent study reported european economic area de bakker pi genetic epidemiology laboratory mrl/lpr mice authors’ original file autoimmune diseases illumina goldengate assay central part biomed central elevated expression level ten million permutations hardy-weinberg equilibrium antibody levels fluctuate cunninghame graham ds gomez-reino jj opposed independent effects o'shea jj watford wt

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Crow MK: Interferon-α: a new target for therapy in systemic lupus erythematosus?

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         headline:Role of STAT4 polymorphisms in systemic lupus erythematosus in a Japanese population: a case-control association study of the STAT1-STAT4region
         description:Recent studies identified STAT4 (signal transducers and activators of transcription-4) as a susceptibility gene for systemic lupus erythematosus (SLE). STAT1 is encoded adjacently to STAT4 on 2q32.2-q32.3, upregulated in peripheral blood mononuclear cells from SLE patients, and functionally relevant to SLE. This study was conducted to test whether STAT4 is associated with SLE in a Japanese population also, to identify the risk haplotype, and to examine the potential genetic contribution of STAT1. To accomplish these aims, we carried out a comprehensive association analysis of 52 tag single nucleotide polymorphisms (SNPs) encompassing the STAT1-STAT4 region. In the first screening, 52 tag SNPs were selected based on HapMap Phase II JPT (Japanese in Tokyo, Japan) data, and case-control association analysis was carried out on 105 Japanese female patients with SLE and 102 female controls. For associated SNPs, additional cases and controls were genotyped and association was analyzed using 308 SLE patients and 306 controls. Estimation of haplotype frequencies and an association study using the permutation test were performed with Haploview version 4.0 software. Population attributable risk percentage was estimated to compare the epidemiological significance of the risk genotype among populations. In the first screening, rs7574865, rs11889341, and rs10168266 in STAT4 were most significantly associated (P < 0.01). Significant association was not observed for STAT1. Subsequent association studies of the three SNPs using 308 SLE patients and 306 controls confirmed a strong association of the rs7574865T allele (SLE patients: 46.3%, controls: 33.5%, P = 4.9 × 10-6, odds ratio 1.71) as well as TTT haplotype (rs10168266/rs11889341/rs7574865) (P = 1.5 × 10-6). The association was stronger in subgroups of SLE with nephritis and anti-double-stranded DNA antibodies. Population attributable risk percentage was estimated to be higher in the Japanese population (40.2%) than in Americans of European descent (19.5%). The same STAT4 risk allele is associated with SLE in Caucasian and Japanese populations. Evidence for a role of STAT1 in genetic susceptibility to SLE was not detected. The contribution of STAT4 for the genetic background of SLE may be greater in the Japanese population than in Americans of European descent.
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            Nephritis
            Systemic Lupus Erythematosus Patient
            Japanese Population
            Risk Genotype
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            Orthopedics
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      description:Recent studies identified STAT4 (signal transducers and activators of transcription-4) as a susceptibility gene for systemic lupus erythematosus (SLE). STAT1 is encoded adjacently to STAT4 on 2q32.2-q32.3, upregulated in peripheral blood mononuclear cells from SLE patients, and functionally relevant to SLE. This study was conducted to test whether STAT4 is associated with SLE in a Japanese population also, to identify the risk haplotype, and to examine the potential genetic contribution of STAT1. To accomplish these aims, we carried out a comprehensive association analysis of 52 tag single nucleotide polymorphisms (SNPs) encompassing the STAT1-STAT4 region. In the first screening, 52 tag SNPs were selected based on HapMap Phase II JPT (Japanese in Tokyo, Japan) data, and case-control association analysis was carried out on 105 Japanese female patients with SLE and 102 female controls. For associated SNPs, additional cases and controls were genotyped and association was analyzed using 308 SLE patients and 306 controls. Estimation of haplotype frequencies and an association study using the permutation test were performed with Haploview version 4.0 software. Population attributable risk percentage was estimated to compare the epidemiological significance of the risk genotype among populations. In the first screening, rs7574865, rs11889341, and rs10168266 in STAT4 were most significantly associated (P < 0.01). Significant association was not observed for STAT1. Subsequent association studies of the three SNPs using 308 SLE patients and 306 controls confirmed a strong association of the rs7574865T allele (SLE patients: 46.3%, controls: 33.5%, P = 4.9 × 10-6, odds ratio 1.71) as well as TTT haplotype (rs10168266/rs11889341/rs7574865) (P = 1.5 × 10-6). The association was stronger in subgroups of SLE with nephritis and anti-double-stranded DNA antibodies. Population attributable risk percentage was estimated to be higher in the Japanese population (40.2%) than in Americans of European descent (19.5%). The same STAT4 risk allele is associated with SLE in Caucasian and Japanese populations. Evidence for a role of STAT1 in genetic susceptibility to SLE was not detected. The contribution of STAT4 for the genetic background of SLE may be greater in the Japanese population than in Americans of European descent.
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         Nephritis
         Systemic Lupus Erythematosus Patient
         Japanese Population
         Risk Genotype
         Rheumatology
         Orthopedics
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            name:Takikawa Municipal Hospital
            address:
               name:Department of Medicine, Takikawa Municipal Hospital, Takikawa, Japan
               type:PostalAddress
            type:Organization
      name:Minori Koga
      affiliation:
            name:University of Tsukuba
            address:
               name:Department of Medical Genetics, Doctoral Program in Life System Medical Sciences, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tsukuba, Japan
               type:PostalAddress
            type:Organization
      name:Tadao Arinami
      affiliation:
            name:University of Tsukuba
            address:
               name:Department of Medical Genetics, Doctoral Program in Life System Medical Sciences, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tsukuba, Japan
               type:PostalAddress
            type:Organization
      name:Robert R Graham
      affiliation:
            name:Genentech, Inc.
            address:
               name:Genentech, Inc., South San Francisco, USA
               type:PostalAddress
            type:Organization
      name:Geoffrey Hom
      affiliation:
            name:Genentech, Inc.
            address:
               name:Genentech, Inc., South San Francisco, USA
               type:PostalAddress
            type:Organization
      name:Yoshinari Takasaki
      affiliation:
            name:Division of Rheumatology, Department of Internal Medicine
            address:
               name:Division of Rheumatology, Department of Internal Medicine, Tokyo, Japan
               type:PostalAddress
            type:Organization
      name:Hiroshi Hashimoto
      affiliation:
            name:Division of Rheumatology, Department of Internal Medicine
            address:
               name:Division of Rheumatology, Department of Internal Medicine, Tokyo, Japan
               type:PostalAddress
            type:Organization
      name:Timothy W Behrens
      affiliation:
            name:Genentech, Inc.
            address:
               name:Genentech, Inc., South San Francisco, USA
               type:PostalAddress
            type:Organization
      name:Takayuki Sumida
      affiliation:
            name:University of Tsukuba
            address:
               name:Division of Clinical Immunology, Doctoral Program in Clinical Sciences, Graduate School of Comprehensive Human Science, University of Tsukuba, Tsukuba, Japan
               type:PostalAddress
            type:Organization
      name:Naoyuki Tsuchiya
      affiliation:
            name:University of Tsukuba
            address:
               name:Molecular and Genetic Epidemiology Laboratory, Doctoral Program in Life System Medical Sciences, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tsukuba, Japan
               type:PostalAddress
            type:Organization
      email:[email protected]
PostalAddress:
      name:Molecular and Genetic Epidemiology Laboratory, Doctoral Program in Life System Medical Sciences, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tsukuba, Japan
      name:Molecular and Genetic Epidemiology Laboratory, Doctoral Program in Life System Medical Sciences, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tsukuba, Japan
      name:Molecular and Genetic Epidemiology Laboratory, Doctoral Program in Life System Medical Sciences, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tsukuba, Japan
      name:Molecular and Genetic Epidemiology Laboratory, Doctoral Program in Life System Medical Sciences, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tsukuba, Japan
      name:Division of Clinical Immunology, Doctoral Program in Clinical Sciences, Graduate School of Comprehensive Human Science, University of Tsukuba, Tsukuba, Japan
      name:Division of Clinical Immunology, Doctoral Program in Clinical Sciences, Graduate School of Comprehensive Human Science, University of Tsukuba, Tsukuba, Japan
      name:Division of Clinical Immunology, Doctoral Program in Clinical Sciences, Graduate School of Comprehensive Human Science, University of Tsukuba, Tsukuba, Japan
      name:Division of Clinical Immunology, Doctoral Program in Clinical Sciences, Graduate School of Comprehensive Human Science, University of Tsukuba, Tsukuba, Japan
      name:Division of Clinical Immunology, Doctoral Program in Clinical Sciences, Graduate School of Comprehensive Human Science, University of Tsukuba, Tsukuba, Japan
      name:Department of Medicine, Takikawa Municipal Hospital, Takikawa, Japan
      name:Department of Medical Genetics, Doctoral Program in Life System Medical Sciences, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tsukuba, Japan
      name:Department of Medical Genetics, Doctoral Program in Life System Medical Sciences, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tsukuba, Japan
      name:Genentech, Inc., South San Francisco, USA
      name:Genentech, Inc., South San Francisco, USA
      name:Division of Rheumatology, Department of Internal Medicine, Tokyo, Japan
      name:Division of Rheumatology, Department of Internal Medicine, Tokyo, Japan
      name:Genentech, Inc., South San Francisco, USA
      name:Division of Clinical Immunology, Doctoral Program in Clinical Sciences, Graduate School of Comprehensive Human Science, University of Tsukuba, Tsukuba, Japan
      name:Molecular and Genetic Epidemiology Laboratory, Doctoral Program in Life System Medical Sciences, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tsukuba, Japan

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