Rheumatoid arthritis does not share most of the newly identified systemic lupus erythematosus genetic factors

Abstract

Objective. Rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) share some genetic factors such as HLA, PTPN22, STAT4, and 6q23. The aim of this study was to determine whether 9 other SLE genetic factors are also implicated in RA susceptibility.Methods. A characteristic single-nucleotide polymorphism (SNP) in each of 9 genetic factors, ITGAM (rs1143679), C8orf13-BLK (rs13277113), TYK2 (rs2304256), 1q25.1 (rs10798269), PXK (rs6445975), KIAA1542 (rs4963128), MECP2 (rs17435), BANK1 (rs17266594), and LY9 (rs509749), was studied in 1,635 patients with RA and 1,906 control subjects from Spain. The rs7574865 SNP in STAT4 was also included. Analyses were conducted globally and after stratification by sex and clinical features (anti-cyclic citrullinated peptide and rheumatoid factor, shared epitope, rheumatoid nodules, radiographic changes, sicca syndrome, and pneumonitis).Results. No association was observed between RA and any of the 9 newly identified SLE genetic factors. A meta-analysis using previous data was consistent with these results. In addition, there were no significant differences between individuals with and those without each of the clinical features analyzed, except the frequency of the minor allele in the C8orf13-BLK locus that was decreased in patients with sicca syndrome (14.6% versus 22.4% in controls; P ‫؍‬ 0.003).Conclusion. None of the 9 recently identified SLE risk factors showed association with RA. Therefore, common genetic factors affecting the pathogenesis of these 2 disorders seem to be limited, revealing that the genetic component contributes to the different expression of these diseases.Rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) share a complex etiology encom-

Lack of association between TYK2 and STAT3 genes and Crohn’s disease in the Malaysian population

“…While the homozygous genotype was absent in our results, this was due to the low frequency of the minor A allele. Similar observations have also been reported in the normal sampling of subjects in various other studies, i.e., Spanish (0.269), Japanese (0.38 and 0.345), Caucasians (0.25), and Malaysians (0.255) (Cunninghame Graham et al, 2007;Sato et al, 2009;Suarez-Gestal et al, 2009;Kyogoku et al, 2009, respectively). TYK2 rs2304256 is essentially a missense polymorphism in exon 8; hence, it is possible that while we did not observe any association with CD in isolation, it could be present on a number of neutrally transmitted low-frequency haplotypes in relation to other TYK2 SNPs.…”

The +1858C/T PTPN22 gene polymorphism confers genetic susceptibility to rheumatoid arthritis in Mexican population from the Western Mexico

“…LYP is also expressed in other cells types like B cells, monocytes, neutrophils and dendritic cells [12]. The presence of the +1858T allele, affects LYP function, resulting in a loss of function protein [1,5,9,10], that are unable to regulates the T cell activation leading to a hyperresponsiveness phenotype of T, B and also dendritic cells [10]. Under these conditions, B lymphocytes could produces increasing amounts of anti-CCP antibodies, leading to a vicious circle of inflammation and conditioning an immunologic milieu favoring the emergence of autoimmune diseases like RA [10,27].…”

“…The genetic background of the systemic autoimmune diseases such as RA is complex and likely involves many genes which encoding proteins with significant functions in the regulation of immune response [1,4]. Likewise, loss of tolerance to self-antigens, which leads to stimulation of lymphocytes and other immune cells, release of cytokines, activation of complement and the production of autoantibodies, contributes to the pathogenesis of the RA [5]. Genetic factors are thought to be responsible for up 50-60% of the predisposition to RA [6].…”

TYK2 rs34536443 polymorphism is associated with a decreased susceptibility to endometriosis-related infertility

“…TYK2 protein is part of the janus kinase (JAK) that binds to the type I interferon-a receptor (IFNAR) on the cell surface of IFN-producing cells, and have crucial importance in the etiology of autoimmune and inflammatory diseases [14]. Many polymorphisms of the TYK2 gene have been identified, and recently, a number of case-control studies were conducted to investigate the association of these polymorphisms with autoimmune and inflammatory diseases [15][16][17][18][19][20][21][22][23][24][25][26], with conflicting results.…”