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      Prognostic significance of high-mobility group box protein 1 genetic polymorphisms in rheumatoid arthritis disease outcome

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          Abstract

          Rheumatoid arthritis (RA) is a systemic inflammatory disease that causes chronic inflammation of the joints. Analysis of genetic variants offers promise for guiding treatment and improving outcomes in RA. High-mobility group box protein 1 (HMGB1) is a ubiquitous nuclear protein found in all mammal eukaryotic cells that participates in several biological functions including immune response, cell survival and apoptosis. We investigated the effects of HMGB1 gene polymorphisms on the risk of RA disease progression in a cohort of Chinese Han individuals. Four single nucleotide polymorphisms (SNPs) from the HMGB1 gene were selected and genotyped in 232 patients with RA and 353 healthy controls. We found that having one C allele in rs1360485 and one G allele in rs2249825 polymorphisms lowered the risk of RA in females. Moreover, among healthy controls, those who bore the C/G/T haplotype at SNPs rs1360485, rs2249825 and rs1412125 were at reduced risk of developing RA by 0.13-fold ( p <0.05). This is the first report to examine the risk factors associated with HMGB1 SNPs in the development of RA disease in the Chinese Han population.

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          Regulation of DNA-dependent activities by the functional motifs of the high-mobility-group chromosomal proteins.

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            A highly significant association between a COMT haplotype and schizophrenia.

            Several lines of evidence have placed the catechol-O-methyltransferase (COMT) gene in the limelight as a candidate gene for schizophrenia. One of these is its biochemical function in metabolism of catecholamine neurotransmitters; another is the microdeletion, on chromosome 22q11, that includes the COMT gene and causes velocardiofacial syndrome, a syndrome associated with a high rate of psychosis, particularly schizophrenia. The interest in the COMT gene as a candidate risk factor for schizophrenia has led to numerous linkage and association analyses. These, however, have failed to produce any conclusive result. Here we report an efficient approach to gene discovery. The approach consists of (i) a large sample size-to our knowledge, the present study is the largest case-control study performed to date in schizophrenia; (ii) the use of Ashkenazi Jews, a well defined homogeneous population; and (iii) a stepwise procedure in which several single nucleotide polymorphisms (SNPs) are scanned in DNA pools, followed by individual genotyping and haplotype analysis of the relevant SNPs. We found a highly significant association between schizophrenia and a COMT haplotype (P=9.5x10-8). The approach presented can be widely implemented for the genetic dissection of other common diseases.
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              Efficacy and safety of sirukumab in patients with active rheumatoid arthritis refractory to anti-TNF therapy (SIRROUND-T): a randomised, double-blind, placebo-controlled, parallel-group, multinational, phase 3 study

              Sirukumab, a human monoclonal antibody that selectively binds to the interleukin-6 cytokine with high affinity, is under development for the treatment of rheumatoid arthritis and other diseases. We aimed to assess the efficacy and safety of sirukumab for rheumatoid arthritis in a phase 3 study (SIRROUND-T).
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                Author and article information

                Journal
                Int J Med Sci
                Int J Med Sci
                ijms
                International Journal of Medical Sciences
                Ivyspring International Publisher (Sydney )
                1449-1907
                2017
                2 November 2017
                : 14
                : 13
                : 1382-1388
                Affiliations
                [1 ]Department of Orthopedics, Affiliated Dongyang Hospital of Wenzhou Medical University, Dongyang, Zhejiang, China;
                [2 ]Physical Education Office, Tunghai University, Taichung, Taiwan;
                [3 ]Sports Recreation and Health Management Continuing Studies, Tunghai University, Taichung, Taiwan;
                [4 ]Graduate Institute of Biomedical Science, China Medical University, Taichung, Taiwan;
                [5 ]Department of Biomedical Sciences Laboratory, Affiliated Dongyang Hospital of Wenzhou Medical University, Dongyang, Zhejiang, China;
                [6 ]Division of Immunology and Rheumatology, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan;
                [7 ]Graduate Institute of Clinical Medical Science, China Medical University, Taichung, Taiwan;
                [8 ]School of Medicine, China Medical University, Taichung, Taiwan;
                [9 ]Department of Orthopedic Surgery, China Medical University Hospital, Taichung, Taiwan;
                [10 ]Department of Biotechnology, College of Health Science, Asia University, Taichung, Taiwan.
                Author notes
                ✉ Corresponding author: Chih-Hsin Tang, PhD, Graduate Institute of Biomedical Science, China Medical University E-mail: chtang@ 123456mail.cmu.edu.tw

                * These authors have contributed equally to this work

                Competing Interests: The authors have declared that no competing interest exists.

                Article
                ijmsv14p1382
                10.7150/ijms.21773
                5707755
                840eeb22-305f-49e8-953f-3c5def7cc645
                © Ivyspring International Publisher

                This is an open access article distributed under the terms of the Creative Commons Attribution (CC BY-NC) license ( https://creativecommons.org/licenses/by-nc/4.0/). See http://ivyspring.com/terms for full terms and conditions.

                History
                : 5 July 2017
                : 11 October 2017
                Categories
                Research Paper

                Medicine
                hmgb1,rheumatoid arthritis,snp,susceptibility.
                Medicine
                hmgb1, rheumatoid arthritis, snp, susceptibility.

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