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. 2019 Mar;15(2):531-536.
doi: 10.5114/aoms.2018.76946. Epub 2018 Jul 5.

Lack of association of -863C/A (rs1800630) polymorphism of tumor necrosis factor-a gene with rheumatoid arthritis

Tayyaba Sadaf  1 , Peter John  1 , Attya Bhatti  1 , Javaid M Malik  2
Affiliations

Lack of association of -863C/A (rs1800630) polymorphism of tumor necrosis factor-a gene with rheumatoid arthritis

Tayyaba Sadaf et al. Arch Med Sci. 2019 Mar.

Abstract

Introduction: Multifunctional pro-inflammatory cytokine tumor necrosis factor-α (TNF-α) has been implicated in a variety of inflammatory diseases including rheumatoid arthritis (RA). TNF-α polymorphisms are mostly located in its promoter region and play a significant role in disease susceptibility and severity. We therefore sought to investigate TNFA -863C/A (rs1800630) polymorphism association with RA activity in our Pakistani study group.

Material and methods: A total of 268 human subjects were enrolled. Among them, 134 were RA patients and 134 were controls. In this study the physical parameters of RA patients were collected, and the disease activity was measured by DAS28. The genotypes were determined following the allele-specific PCR along with the pre-requisite internal amplification controls. Subsequently, data were analyzed statistically for any significant association including χ2/Fisher's exact test using GraphPad prism 6 software.

Results: We found that the TNF-α -863 C/A (rs1800630) variant was not differentially segregated between cases and controls in either genotype frequency, with χ2 of 2.771 and a p-value of 0.2502, or allele frequency, with χ2 of 2.741 and a p-value of 0.0978, with an odds ratio (95% CI) of 0.7490 (0.5317-1.055).

Conclusions: The lack of positive association of TNF-α -863(rs1800630) polymorphism in our study group implies that TNF-α -863 polymorphism is not a susceptible marker to RA and cannot serve as a genetic factor for screening RA patients in Pakistan. There might be other factors that may influence disease susceptibility. However, further investigations on additional larger and multi-regional population samples are required to determine the consequences of genetic variations for disease prognosis.

Keywords: association study; polymorphism; rheumatoid arthritis; tumor necrosis factor-alpha.

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Conflict of interest statement

The authors declare no conflict of interest. References1CrossMSmithEHoyDThe global burden of rheumatoid arthritis: estimates from the Global Burden of Disease 2010 studyAnn Rheum Dis201473131622245501732AlamanosYDrososAAEpidemiology of adult rheumatoid arthritisAutoimmun Rev200541306158234983FarooqiAGibsonTPrevalence of the major rheumatic disorders in the adult population of north PakistanBr J Rheumatol199837491596510744KlareskogLPadyukovLRönnelidJAlfredssonLGenes, environment and immunity in the development of rheumatoid arthritisCurr Opin Immunol2006186505170105895BegovichABCarltonVEHonigbergLAA missense single-nucleotide polymorphism in a gene encoding a protein tyrosine phosphatase (PTPN22) is associated with rheumatoid arthritisAm J Hum Genet2004753307152087816PawlikAHerczyńskaMKurzawskiMIL-1beta, IL-6, and TNF gene polymorphisms do not affect the treatment outcome of rheumatoid arthritis patients with leflunomidePharmacol Rep2009612817194439407OtaMKatsuyamaYKimuraAA second susceptibility gene for developing rheumatoid arthritis in the human MHC is localized within a 70-kb interval telomeric of the TNF genes in the HLA class III regionGenomics20017126370111707438ZanelliEJonesGPascualMThe telomeric part of the HLA region predisposes to rheumatoid arthritis independently of the class II lociHum Immunol2001627584111657179JawaheerDLiWGrahamRRDissecting the genetic complexity of the association between human leukocyte antigens and rheumatoid arthritisAm J Hum Genet200271585941218177610FonsecaJECavaleiroJTelesJContribution for new genetic markers of rheumatoid arthritis activity and severity: sequencing of the tumor necrosis factor-alpha gene promoterArthritis Res Ther20079R371740849211BayleyJPOttenhoffTHVerweijCLIs there a future for TNF promoter polymorphisms?Genes Immun20045315291497354812UdalovaIARichardsonADenysAFunctional consequences of a polymorphism affecting NF-kappaB p50-p50 binding to the TNF promoter regionMol Cell Biol200020911391109406313SkoogTvan’t HooftFMKallinBA common functional polymorphism (C → A substitution at position− 863) in the promoter region of the tumour necrosis factor-alpha (TNF-alpha) gene associated with reduced circulating levels of TNF-alphaHum Mol Genet19998144391040099114UdalovaIARichardsonAAckermanHWordsworthPKwiatkowskiDAssociation of accelerated erosive rheumatoid arthritis with a polymorphism that alters NF-kappaB binding to the TNF promoter regionRheumatology (Oxford)20024183011209624015GambhirDLawrenceAAggarwalAMisraRMandalSKNaikSAssociation of tumor necrosis factor alpha and IL-10 promoter polymorphisms with rheumatoid arthritis in North Indian populationRheumatol Int201030121171977972416JohnPBhattiAul AinNIqbalTSadafTMalikJMCase-control study of vitamin D receptor gene polymorphism in Pakistani rheumatoid arthritis patientsRev Bras Reumatol Engl Ed20175763362917370317SadafTJohnPBhattiALack of tumor necrosis factor alpha gene polymorphism-857c/t (rs1799724) association in Pakistani rheumatoid arthritis patientsInt J Rheum Dis2016191119252712678418KibbeWAOligoCalc: an online oligonucleotide properties calculatorNucleic Acids Res200735Suppl 2W4361745234419MacGregorAJSniederHRigbyASCharacterizing the quantitative genetic contribution to rheumatoid arthritis using data from twinsArthritis Rheum2000433071064369720JawaheerDSeldinMFAmosCIScreening the genome for rheumatoid arthritis susceptibility genes: a replication study and combined analysis of 512 multicase familiesArthritis Rheum200348906161268753221MacKayKEyreSMyerscoughAWhole-genome linkage analysis of rheumatoid arthritis susceptibility loci in 252 affected sibling pairs in the United KingdomArthritis Rheum20024663291192039822FisherSALanchburyJSLewisCMMeta-analysis of four rheumatoid arthritis genome-wide linkage studies: confirmation of a susceptibility locus on chromosome 16Arthritis Rheum200348120061274689223VriesNDTijssenHRielPLPutteLBReshaping the shared epitope hypothesis: HLA-associated risk for rheumatoid arthritis is encoded by amino acid substitutions at positions 67-74 of the HLA-DRB1 moleculeArthritis Rheum20024692181195396824YenJHChenCJTsaiWCTumor necrosis factor promoter polymorphisms in patients with rheumatoid arthritis in TaiwanJ Rheumatol2001281788921150858025RainaPMatharooKKumarASarangalPSharmaRBhanwerAJSAssociation of tumor necrosis factor-alpha –308 G>A polymorphism with rheumatoid arthritis in two north Indian cohortsArch Rheumatol201429241926FonsecaJECavaleiroJTelesJContribution for new genetic markers of rheumatoid arthritis activity and severity: sequencing of the tumor necrosis factor-alpha gene promoterArthritis Res Ther20079R371740849227KirkhamBWLassereMNEdmondsJPSynovial membrane cytokine expression is predictive of joint damage progression in rheumatoid arthritis: a two-year prospective study (the DAMAGE study cohort)Arthritis Rheum2006541122311657244728RichardsonASisay-JoofFAckermanHNucleotide diversity of the TNF gene region in an African villageGenes Immun2001234381160779129BayleyJPOttenhoffTHVerweijCLIs there a future for TNF promoter polymorphisms?Genes Immun20045315291497354830LisKKuzawińskaOBałkowiec-IskraETumor necrosis factor inhibitors – state of knowledgeArch Med Sci2014101175852562485631ZhengXZhouJXiaYThe role of TNF-alpha in regulating ketamine-induced hippocampal neurotoxicityArch Med Sci20151112963022678809332El-TahanRRGhoneimAMEl-MashadNTNF-alpha gene polymorphisms and expressionSpringerplus2016515082765208133De VriesNTakPPThe response to anti-TNF-alpha treatment: gene regulation at the bedsideRheumatology (Oxford)20054470571585518634FonsecaJECarvalhoTCruzMPolymorphism at position –308 of the tumour necrosis factor α gene and rheumatoid arthritis pharmacogeneticsAnn Rheum Dis20056479341583406835SashioHTamuraKItoRPolymorphisms of the TNF gene and the TNF receptor superfamily member 1B gene are associated with susceptibility to ulcerative colitis and Crohn’s disease, respectivelyImmunogenetics200253102071190467836LiHGroopLNilssonAWengJTuomiTA combination of human leukocyte antigen DQB1* 02 and the tumor necrosis factor alpha promoter G308A polymorphism predisposes to an insulin-deficient phenotype in patients with type 2 diabetesJ Clin Endocrinol Metab2003882767741278888637CorreaPAGomezLMCadenaJAnayaJMAutoimmunity and tuberculosis. Opposite association with TNF polymorphismJ Rheumatol200532219241569308038HöhlerTGrossmannSStradmann-BellinghausenBDifferential association of polymorphisms in the TNFalpha region with psoriatic arthritis but not psoriasisAnn Rheum Dis20026121381183042539BaldingJKaneDLivingstoneWCytokine gene polymorphisms: association with psoriatic arthritis susceptibility and severityArthritis Rheum2003481408131274691440RahmanPSiannisFButtCTNFalpha polymorphisms and risk of psoriatic arthritisAnn Rheum Dis200665919231628409841MurdacaGGulliRSpanòFTNF-alpha gene polymorphisms: association with disease susceptibility and response to anti-TNF-alpha treatment in psoriatic arthritisJ Invest Dermatol2014134250392459466942Jiménez-MoralesSVelázquez-CruzRRamírez-BelloJTumor necrosis factor-alpha is a common genetic risk factor for asthma, juvenile rheumatoid arthritis, and systemic lupus erythematosus in a Mexican pediatric populationHum Immunol20097025161948084343ModestoCPatiño-GarcíaASotillo-PiñeiroETNF- alpha promoter gene polymorphisms in Spanish children with persistent oligoarticular and systemic-onset juvenile idiopathic arthritisScand J Rheumatol20053445141639376744GonzálezSRodrigoLMartínez-BorraJTNF-alpha -308A promoter polymorphism is associated with enhanced TNF-alpha production and inflammatory activity in Crohn’s patients with fistulizing diseaseAm J Gastroenterol200398110161280983445UglialoroAMTurbayDPesaventoPAIdentification of three new single nucleotide polymorphisms in the human tumor necrosis factor-alpha gene promoterTissue Antigens19985235967982059946SekiNKamizonoSYamadaAPolymorphisms in the 5′-flanking region of tumor necrosis factor-alpha gene in patients with rheumatoid arthritisTissue Antigens199954194710488748

Figures

Figure 1
Figure 1
Distribution of different genotypes and alleles of TNF-α gene promoter –863C/A (rs1800630) polymorphism among our study groups (cases and controls). A – p = 0.2502 with χ2 = 2.771; B – p = 0.0978 with χ2 = 2.741. Calculation using χ2/Fisher exact test shows no statistically significant difference
See this image and copyright information in PMC

References

    1. Cross M, Smith E, Hoy D, et al. The global burden of rheumatoid arthritis: estimates from the Global Burden of Disease 2010 study. Ann Rheum Dis. 2014;73:1316–22. - PubMed
    1. Alamanos Y, Drosos AA. Epidemiology of adult rheumatoid arthritis. Autoimmun Rev. 2005;4:130–6. - PubMed
    1. Farooqi A, Gibson T. Prevalence of the major rheumatic disorders in the adult population of north Pakistan. Br J Rheumatol. 1998;37:491–5. - PubMed
    1. Klareskog L, Padyukov L, Rönnelid J, Alfredsson L. Genes, environment and immunity in the development of rheumatoid arthritis. Curr Opin Immunol. 2006;18:650–5. - PubMed
    1. Begovich AB, Carlton VE, Honigberg LA, et al. A missense single-nucleotide polymorphism in a gene encoding a protein tyrosine phosphatase (PTPN22) is associated with rheumatoid arthritis. Am J Hum Genet. 2004;75:330–7. - PMC - PubMed