Abstract
Advances in genomics and proteomics aid the identification of genes associated with various diseases. Genome-Wide Association Studies (GWAS) have identified multiple loci as risk alleles for susceptibility to Rheumatoid Arthritis (RA). A bisection of RA risk can be attributed to genetic factors. Over 100 associated genetic loci that encompass immune regulatory factors have been found to be linked with RA. Aberrant Single Nucleotide Polymorphisms (SNPs) and alternative splicing mechanisms in such loci induce RA. These aberrations are viewed as potential therapeutic targets due to their association with a multitude of diseases. This review presents a few imperious genes whose alterations can cause severe bone deformities culminating in RA.
Keywords: Rheumatoid arthritis, alternative splicing, bone deformation, inflammation, single nucleotide polymorphisms, autoimmunity.
Graphical Abstract
[http://dx.doi.org/10.1093/rheumatology/kes113] [PMID: 22718924]
[http://dx.doi.org/10.1038/sj.gene.6364045] [PMID: 14749714]
[http://dx.doi.org/10.1016/j.jaut.2009.12.009] [PMID: 20080387]
[http://dx.doi.org/10.1016/S0140-6736(10)60826-4] [PMID: 20870100]
[http://dx.doi.org/10.1016/S0378-1119(99)00219-X] [PMID: 10395891]
[http://dx.doi.org/10.1002/wrna.1276] [PMID: 25630614]
[http://dx.doi.org/10.1155/2013/703568] [PMID: 23766705]
[http://dx.doi.org/10.1038/nbt964] [PMID: 15122293]
[http://dx.doi.org/10.1007/s10522-004-2567-y] [PMID: 15547317]
[http://dx.doi.org/10.1038/ni904] [PMID: 12612578]
[http://dx.doi.org/10.1084/jem.20030152] [PMID: 14676299]
[http://dx.doi.org/10.1677/jme.1.02072] [PMID: 16901927]
[http://dx.doi.org/10.1172/JCI11679] [PMID: 11120765]
[http://dx.doi.org/10.1016/j.str.2005.10.005] [PMID: 16407075]
[http://dx.doi.org/10.1016/0925-4773(96)00539-4] [PMID: 8817449]
[PMID: 10702024]
[http://dx.doi.org/10.4049/jimmunol.177.5.3133] [PMID: 16920951]
[http://dx.doi.org/10.1016/S1097-2765(03)00043-1] [PMID: 12620233]
[http://dx.doi.org/10.1038/nri2061] [PMID: 17380159]
[http://dx.doi.org/10.1016/j.micinf.2009.04.002] [PMID: 19371792]
[http://dx.doi.org/10.1016/j.humimm.2011.06.011] [PMID: 21763379]
[http://dx.doi.org/10.1016/j.jdermsci.2009.09.010] [PMID: 19880293]
[http://dx.doi.org/10.1177/0961203310382428] [PMID: 21078762]
[http://dx.doi.org/10.1111/j.1365-2249.2010.04229.x] [PMID: 20942809]
[http://dx.doi.org/10.1016/j.fertnstert.2011.03.033] [PMID: 21481380]
[http://dx.doi.org/10.1196/annals.1361.125] [PMID: 16126962]
[http://dx.doi.org/10.1016/j.cancergencyto.2008.12.005] [PMID: 19264232]
[http://dx.doi.org/10.1038/ng0896-472] [PMID: 8696345]
[http://dx.doi.org/10.1210/jc.86.2.626] [PMID: 11158020]
[http://dx.doi.org/10.1210/jc.2005-0686] [PMID: 16278270]
[http://dx.doi.org/10.1073/pnas.95.18.10746] [PMID: 9724775]
[http://dx.doi.org/10.1038/ng.175] [PMID: 18587394]
[http://dx.doi.org/10.1016/j.humimm.2005.06.001] [PMID: 16216670]
[http://dx.doi.org/10.3899/jrheum.131381] [PMID: 25448791]
[http://dx.doi.org/10.1016/j.ejr.2014.06.004]
[http://dx.doi.org/10.1111/j.1600-0463.2011.02848.x] [PMID: 22515293]
[http://dx.doi.org/10.1111/j.1365-2567.2012.03591.x] [PMID: 22862552]
[http://dx.doi.org/10.1038/ng1323] [PMID: 15004560]
[http://dx.doi.org/10.1038/sj.gene.6364261] [PMID: 16163373]
[http://dx.doi.org/10.1002/art.21294] [PMID: 16145680]
[http://dx.doi.org/10.1002/art.20771] [PMID: 15641066]
[http://dx.doi.org/10.1086/422827] [PMID: 15208781]
[http://dx.doi.org/10.1038/sj.gene.6364255] [PMID: 16107870]
[http://dx.doi.org/10.1086/498651] [PMID: 16380915]
[http://dx.doi.org/10.1002/art.21049] [PMID: 15934099]
[http://dx.doi.org/10.1002/art.21126] [PMID: 15986352]
[http://dx.doi.org/10.1086/423790] [PMID: 15273934]
[http://dx.doi.org/10.1177/0961203310381774] [PMID: 21078766]
[http://dx.doi.org/10.1111/j.1399-0039.2008.01115.x] [PMID: 18764813]
[http://dx.doi.org/10.2337/diabetes.53.11.3020] [PMID: 15504986]
[http://dx.doi.org/10.1007/s00281-010-0201-4] [PMID: 20204370]
[http://dx.doi.org/10.1186/gm301] [PMID: 22264340]
[http://dx.doi.org/10.1002/art.30145] [PMID: 21279993]
[http://dx.doi.org/10.1371/journal.pone.0024292] [PMID: 21949702]
[http://dx.doi.org/10.1086/468189] [PMID: 16175503]
[http://dx.doi.org/10.3899/jrheum.110361] [PMID: 21965649]
[http://dx.doi.org/10.1371/journal.pone.0013544] [PMID: 20975833]
[http://dx.doi.org/10.1371/journal.pone.0033067] [PMID: 22427951]
[http://dx.doi.org/10.1038/nrc968] [PMID: 12509766]
[http://dx.doi.org/10.1038/nm0897-917] [PMID: 9256286]
[http://dx.doi.org/10.1002/jcp.10327] [PMID: 12942537]
[http://dx.doi.org/10.1186/1476-4598-4-11] [PMID: 15743529]
[http://dx.doi.org/10.1016/j.bbrc.2003.12.178] [PMID: 14741722]
[PMID: 10626797]
[http://dx.doi.org/10.1016/j.canlet.2006.12.020] [PMID: 17275177]
[http://dx.doi.org/10.1038/sj.cdd.4401091] [PMID: 12478470]
[http://dx.doi.org/10.1074/jbc.M700776200] [PMID: 17613533]
[http://dx.doi.org/10.1042/BJ20100814] [PMID: 20704571]
[http://dx.doi.org/10.1016/j.bbrc.2016.11.094] [PMID: 27865841]
[http://dx.doi.org/10.1038/25141] [PMID: 9859993]
[http://dx.doi.org/10.1016/j.autrev.2017.05.016] [PMID: 28564620]
[http://dx.doi.org/10.1016/j.imlet.2017.11.004] [PMID: 29155234]
[http://dx.doi.org/10.1189/jlb.3A0714-317R] [PMID: 25381389]
[http://dx.doi.org/10.18632/oncotarget.4994] [PMID: 26343374]
[http://dx.doi.org/10.1186/ar4474] [PMID: 24495510]
[http://dx.doi.org/10.1186/s13075-015-0689-z] [PMID: 26160473]
[http://dx.doi.org/10.1186/ar1498] [PMID: 15743483]
[http://dx.doi.org/10.1093/rheumatology/kep467] [PMID: 20147446]
[http://dx.doi.org/10.1038/srep09795] [PMID: 25997820]
[http://dx.doi.org/10.4161/19336918.2014.987587] [PMID: 25482829]
[http://dx.doi.org/10.1007/s12079-009-0075-1] [PMID: 19838819]
[http://dx.doi.org/10.1007/BF01921736] [PMID: 7556567]
[http://dx.doi.org/10.1016/0955-0674(93)90037-Q] [PMID: 7694605]
[http://dx.doi.org/10.1083/jcb.134.6.1499] [PMID: 8830777]
[http://dx.doi.org/10.1615/critrevimmunol.v31.i2.30] [PMID: 21542790]
[http://dx.doi.org/10.1186/ar4105] [PMID: 23193984]
[http://dx.doi.org/10.4049/jimmunol.0903359] [PMID: 20107185]
[http://dx.doi.org/10.1002/jor.20366] [PMID: 17262825]
[http://dx.doi.org/10.1126/science.3283939]
[http://dx.doi.org/10.1096/fj.01-0245com] [PMID: 11772937]
[http://dx.doi.org/10.1210/me.2006-0345] [PMID: 17440046]
[http://dx.doi.org/10.1042/bse0400137] [PMID: 15242344]
[http://dx.doi.org/10.1172/JCI117943] [PMID: 7769088]
[http://dx.doi.org/10.1007/s00018-009-0098-z] [PMID: 19633971]
[http://dx.doi.org/10.1677/jme.1.02183] [PMID: 17242171]
[http://dx.doi.org/10.1677/jme.1.01822] [PMID: 16216909]
[PMID: 2365707]
[PMID: 3192546]
[http://dx.doi.org/10.1210/mend.9.11.8584032] [PMID: 8584032]
[http://dx.doi.org/10.1126/stke.3042005pe48] [PMID: 16204701]
[http://dx.doi.org/10.1016/j.coph.2004.06.009] [PMID: 15525555]
[http://dx.doi.org/10.1164/rccm.200507-1046OC] [PMID: 16387802]
[PMID: 11708406]
[http://dx.doi.org/10.3904/kjim.2005.20.2.146] [PMID: 16134770]
[http://dx.doi.org/10.1055/s-2007-978661] [PMID: 11069204]
[http://dx.doi.org/10.1006/bbrc.1998.9980] [PMID: 9920778]
[PMID: 18165172]
[http://dx.doi.org/10.2741/A306] [PMID: 9634544]
[http://dx.doi.org/10.1016/S0065-230X(08)60101-3] [PMID: 9111868]
[http://dx.doi.org/10.1002/eji.1830120807] [PMID: 7140811]
[PMID: 1537855]
[PMID: 8509359]
[http://dx.doi.org/10.15537/smj.2015.3.9622] [PMID: 25737167]
[http://dx.doi.org/10.1016/S0065-2776(08)60537-4] [PMID: 8379464]
[PMID: 22261341]
[http://dx.doi.org/10.1002/art.10421] [PMID: 12209509]
[PMID: 15083882]
[http://dx.doi.org/10.1016/j.tibs.2008.12.003] [PMID: 19233657]
[http://dx.doi.org/10.1016/j.it.2009.05.007] [PMID: 19643665]
[http://dx.doi.org/10.1038/nature05698] [PMID: 17361131]
[http://dx.doi.org/10.1074/jbc.R800032200] [PMID: 19008218]
[http://dx.doi.org/10.1016/j.bcp.2010.06.044] [PMID: 20599425]
[http://dx.doi.org/10.1042/BJ20071399] [PMID: 17961127]
[http://dx.doi.org/10.1038/nature02794] [PMID: 15258597]
[http://dx.doi.org/10.1016/j.molcel.2010.10.009] [PMID: 21095585]
[http://dx.doi.org/10.1155/2014/492872] [PMID: 24971370]
[http://dx.doi.org/10.1093/rheumatology/kes292] [PMID: 23148088]
[http://dx.doi.org/10.1093/hmg/ddp193] [PMID: 19417005]
[http://dx.doi.org/10.1093/rheumatology/ket473] [PMID: 24489017]
[http://dx.doi.org/10.1146/annurev.med.46.1.443] [PMID: 7598477]
[http://dx.doi.org/10.1056/NEJMra000471] [PMID: 11821512]
[http://dx.doi.org/10.4061/2011/812540] [PMID: 22312471]
[http://dx.doi.org/10.1002/rmb2.12006] [PMID: 29259445]
[http://dx.doi.org/10.3109/03009742.2014.918174] [PMID: 25179669]
[http://dx.doi.org/10.1136/ard.58.1.7] [PMID: 10343533]
[http://dx.doi.org/10.1016/j.rbr.2013.10.006] [PMID: 25627226]
[http://dx.doi.org/10.3390/ijms18071432] [PMID: 28677621]
[http://dx.doi.org/10.1111/j.1399-0039.2005.00341.x] [PMID: 15713218]
[http://dx.doi.org/10.1007/s00005-016-0443-5] [PMID: 28083614]
[http://dx.doi.org/10.1016/j.steroids.2012.10.019] [PMID: 23178257]
[http://dx.doi.org/10.1016/j.cca.2006.02.016] [PMID: 16563362]
[http://dx.doi.org/10.1007/s11033-015-3937-z] [PMID: 26686848]
[http://dx.doi.org/10.1046/j.1365-2370.2001.00233.x] [PMID: 11251690]
[http://dx.doi.org/10.1016/j.sjbs.2014.10.002] [PMID: 26150740]
[http://dx.doi.org/10.1038/sj.onc.1210392] [PMID: 17496909]
[http://dx.doi.org/10.1038/nature00766] [PMID: 12068308]
[http://dx.doi.org/10.1074/jbc.C110.168195] [PMID: 20843808]
[http://dx.doi.org/10.1002/art.39588] [PMID: 26814611]
[http://dx.doi.org/10.1016/j.molimm.2013.02.001] [PMID: 23517740]
[http://dx.doi.org/10.1074/jbc.R800069200] [PMID: 19201757]
[http://dx.doi.org/10.1038/nrurol.2011.44] [PMID: 21487384]
[PMID: 20495735]
[http://dx.doi.org/10.1002/1529-0131(200201)46:1<13:AID-ART497>3.0.CO;2-S] [PMID: 11817584]
[http://dx.doi.org/10.1161/CIRCULATIONAHA.105.573865] [PMID: 16636176]
[http://dx.doi.org/10.1016/j.bbamcr.2009.07.004] [PMID: 19631700]
[http://dx.doi.org/10.1007/s10875-012-9735-7] [PMID: 22767184]
[http://dx.doi.org/10.1038/gene.2012.65] [PMID: 23343931]
[http://dx.doi.org/10.1007/s00296-009-0974-8] [PMID: 19504098]
[PMID: 11824952]
[http://dx.doi.org/10.1186/ar1164] [PMID: 15142265]
[http://dx.doi.org/10.1196/annals.1423.019] [PMID: 17911432]
[http://dx.doi.org/10.1080/03009740310003749] [PMID: 14626631]
[PMID: 8789287]
[http://dx.doi.org/10.1111/j.1749-6632.1998.tb08323.x] [PMID: 9917875]
[http://dx.doi.org/10.1146/annurev.cb.09.110193.001533] [PMID: 8280464]
[http://dx.doi.org/10.1016/j.imbio.2005.09.005] [PMID: 16446172]
[http://dx.doi.org/10.1007/s00296-007-0409-3] [PMID: 17710405]
[PMID: 11508580]
[PMID: 11838837]
[http://dx.doi.org/10.1093/rheumatology/41.2.223] [PMID: 11886974]
[http://dx.doi.org/10.1556/AMicr.51.2004.3.4] [PMID: 15571066]
[http://dx.doi.org/10.1002/art.21750] [PMID: 16572445]
[http://dx.doi.org/10.1155/1994/756247] [PMID: 7614782]
[http://dx.doi.org/10.1111/j.1399-0039.1997.tb02715.x] [PMID: 9027971]
[http://dx.doi.org/10.1016/j.jaut.2004.11.002] [PMID: 15725578]
[http://dx.doi.org/10.1093/rheumatology/keg092] [PMID: 12595628]
[http://dx.doi.org/10.1007/s10067-007-0653-7] [PMID: 17562093]
[http://dx.doi.org/10.1093/nar/gkq1039] [PMID: 21071392]