{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,8]],"date-time":"2025-10-08T22:50:24Z","timestamp":1759963824336},"reference-count":45,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2017,4,4]],"date-time":"2017-04-04T00:00:00Z","timestamp":1491264000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001677","name":"Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale","doi-asserted-by":"publisher","award":["UMRS 940","U1160"],"award-info":[{"award-number":["UMRS 940","U1160"]}],"id":[{"id":"10.13039\/501100001677","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Int J Immunogenetics"],"published-print":{"date-parts":[[2017,6]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p>Nitric oxide synthase (NOS) catalyses the production of nitric oxide (NO) from L\u2010Arginine, which participates in diverse biological processes including inflammation and apoptosis. Macrophages, chondrocytes, osteoblasts and osteoclasts express inducible NOS (iNOS) at the site of synovial inflammation. NO produced at the inflamed joint may contribute to peri\u2010articular bone loss, mediate apoptosis and regulate Th1\/Th2 balance in rheumatoid arthritis (RA). Variations in the promoter region of <jats:italic>NOS<\/jats:italic> gene regulate the nitric oxide synthase expression and <jats:italic>iNOS (NOS2)<\/jats:italic> polymorphisms have been associated with susceptibility to autoimmune disorders. Hence, this study was conducted to identify the possible contributions of <jats:italic>NOS2 \u20101659G\/A, \u20101026C\/A, \u2010277A\/G<\/jats:italic> promoter polymorphisms towards development of RA in South Indian Tamils. A total of 242 (219 females, 23 males) patients with RA (mean age 41.2\u00a0\u00b1\u00a010.9\u00a0years, disease duration 8.5\u00a0\u00b1\u00a04.3\u00a0years) and 279 age\u2010 and sex\u2010matched healthy individuals of South Indian Tamil ethnicity were genotyped for <jats:italic>NOS2 \u20101659C\/T, \u20101026G\/T and \u2010277A\/G<\/jats:italic> promoter polymorphisms by TaqMan chemistry. Nature of disease (erosive or nonerosive), the presence of extra\u2010articular manifestations, seropositivity for rheumatoid factor and anticyclic citrullinated peptide, serum C\u2010reactive protein (CRP) level and response to therapy were assessed for all patients. The three single nucleotide polymorphisms (SNPs) were in Hardy\u2013Weinberg equilibrium. The frequency of GG genotype and G allele of <jats:italic>NOS2\u2010277<\/jats:italic> was higher in patients (<jats:italic>p<\/jats:italic>c<jats:italic>\u00a0<\/jats:italic>=\u00a05.7\u00a0\u00d7\u00a010<jats:sup>\u22129<\/jats:sup>, OR\u00a0=\u00a06.09, 95% CI\u00a0=\u00a03.09\u201312.8 and <jats:italic>p<\/jats:italic>c<jats:italic>\u00a0<\/jats:italic>=\u00a04\u00a0\u00d7\u00a010<jats:sup>\u221213<\/jats:sup>, OR\u00a0=\u00a02.37, 95% CI\u00a0=\u00a02.06\u20133.62, respectively) compared to controls. Similarly, the frequency of <jats:italic>NOS2\u20101026<\/jats:italic> (rs2779249) GT genotype and the T allele was higher in patients with RA (<jats:italic>p<\/jats:italic>c<jats:italic>\u00a0<\/jats:italic>=\u00a0.01, OR\u00a0=\u00a01.61, 95% CI\u00a0=\u00a01.09\u20132.36, and <jats:italic>p<\/jats:italic>c<jats:italic>\u00a0<\/jats:italic>=\u00a0.04, OR\u00a0=\u00a01.40, 95% CI\u00a0=\u00a01.02\u20131.91, respectively). However, no significant difference in frequency of <jats:italic>NOS2\u20101659C\/T<\/jats:italic> polymorphism was observed between patients and controls. None of the studied SNPs were associated with erosive disease, seropositivity or extra\u2010articular manifestations. The <jats:italic>\u2010277A\/G<\/jats:italic> and <jats:italic>\u20101026\u00a0G\/T<\/jats:italic> promoter polymorphisms in <jats:italic>iNOS<\/jats:italic> may confer susceptibility to RA in South Indian Tamils.<\/jats:p>","DOI":"10.1111\/iji.12315","type":"journal-article","created":{"date-parts":[[2017,4,5]],"date-time":"2017-04-05T15:32:23Z","timestamp":1491406343000},"page":"114-121","source":"Crossref","is-referenced-by-count":10,"title":["Polymorphisms in the promoter region of <i>iNOS<\/i> predispose to rheumatoid arthritis in south Indian Tamils"],"prefix":"10.1111","volume":"44","author":[{"given":"V. S.","family":"Negi","sequence":"first","affiliation":[{"name":"Department of Clinical Immunology Jawaharlal Institute of Postgraduate Medical Education and Research (JIPMER)  Puducherry India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"C. M.","family":"Mariaselvam","sequence":"additional","affiliation":[{"name":"Department of Clinical Immunology Jawaharlal Institute of Postgraduate Medical Education and Research (JIPMER)  Puducherry India"},{"name":"INSERM, UMRS, U1160 Saint Louis Hospital  Paris France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"D. P.","family":"Misra","sequence":"additional","affiliation":[{"name":"Department of Clinical Immunology Jawaharlal Institute of Postgraduate Medical Education and Research (JIPMER)  Puducherry India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"N.","family":"Muralidharan","sequence":"additional","affiliation":[{"name":"Department of Clinical Immunology Jawaharlal Institute of Postgraduate Medical Education and Research (JIPMER)  Puducherry India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"C.","family":"Fortier","sequence":"additional","affiliation":[{"name":"Jean Dausset laboratory of Immunology and Immunogenetics and LabExTransplantex Saint Louis Hospital  Paris France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"D.","family":"Charron","sequence":"additional","affiliation":[{"name":"INSERM, UMRS, U1160 Saint Louis Hospital  Paris France"},{"name":"Jean Dausset laboratory of Immunology and Immunogenetics and LabExTransplantex Saint Louis Hospital  Paris France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"R.","family":"Krishnamoorthy","sequence":"additional","affiliation":[{"name":"INSERM, UMRS, U1160 Saint Louis Hospital  Paris France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"R.","family":"Tamouza","sequence":"additional","affiliation":[{"name":"INSERM, UMRS, U1160 Saint Louis Hospital  Paris France"},{"name":"Jean Dausset laboratory of Immunology and Immunogenetics and LabExTransplantex Saint Louis Hospital  Paris France"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2017,4,4]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjp.0706168"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/1529-0131(200112)44:12<2790::AID-ART466>3.0.CO;2-X"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.1780310302"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10067-008-1018-6"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.ejhg.5201422"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00296-015-3401-3"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.gene.6364022"},{"key":"e_1_2_8_9_1","first-page":"240","article-title":"Prevalence of rheumatic diseases in a rural population in western India: A WHO\u2010ILAR COPCORD Study","volume":"49","author":"Chopra A.","year":"2001","journal-title":"Journal of the Association of Physicians of India"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.3109\/03009748709102172"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/0014-2999(94)00672-T"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-2999(02)02338-5"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/ker429"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.rdc.2009.10.001"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1097\/HJH.0b013e3283294bec"},{"key":"e_1_2_8_16_1","first-page":"116","article-title":"Influence of nitric oxide synthase gene polymorphisms on the risk of cardiovascular events in rheumatoid arthritis","volume":"27","author":"Gonzalez\u2010Gay M. 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