Genetic variants near TNFAIP3 on 6q23 are associated with systemic lupus erythematosus

Abstract

SLE is an autoimmune disease influenced by genetic and environmental components. We performed a genome-wide association scan (GWAS) and observed novel association evidence with a variant inTNFAIP3(rs5029939, P = 2.89×10−12, OR = 2.29). We also found evidence of two independent signals of association to SLE risk, including one described in Rheumatoid Arthritis. These results establish that genetic variation inTNFAIP3contributes to differential risk for SLE and RA.

Analysis of 17 autoimmune disease-associated variants in type 1 diabetes identifies 6q23/TNFAIP3 as a susceptibility locus

“…More recently, this gene region has also been associated with SLE in two independent studies. 21,22 In Musone et al 22 three independent associations conferring risk were associated with SLE, including the two SNPs previously associated with RA. However, Graham et al 21 found two independent associations, one of which was previously associated with RA.…”

“…21,22 In Musone et al 22 three independent associations conferring risk were associated with SLE, including the two SNPs previously associated with RA. However, Graham et al 21 found two independent associations, one of which was previously associated with RA. Further analyses of the region will be required to establish if the associations in all three diseases are due to the same or different variant(s).…”

“…18 We selected single nucleotide polymorphisms (SNPs) for genotyping that had shown a convincing evidence of association with at least one other autoimmune disease from genome-wide association scans published over the past 2 years. We genotyped SNPs from the genes: CD58 (rs12044852) which has been associated with multiple sclerosis; 8 STAT3 (rs3816769) which has been associated with CD; 7 IL1A (rs17561) and ERAP1, previously called ARTS1 (rs30187) which have been associated with AS; 15,17 MMEL1-TNFRSF14 (rs3890745), CDK6 (rs42041), the 7q23 gene desert (rs11761231), CCL21 (rs2812378), TRAF1/C5 (rs3761847), KIF5A(rs1678542) and CD40 (rs4810485), which have been associated with RA; 7,12,19 BANK1 (rs10516487), FAM167A previously called C8orf13 (rs13277113) and ITGAM (rs9888739) which have been associated with SLE [9][10][11]20 and STAT4 (rs7574865) and TNFAIP3 (rs6920220 and rs10499194) which have been associated with both RA and SLE 13,14,16,21,22 (See Table 1 for full gene names).…”

Differential contribution of CDKAL1 variants to psoriasis, Crohn's disease and type II diabetes

“…4,5 More recently, the advent of genome-wide association scans has allowed the identification of several non-MHC susceptibility genes, including IL12B, IL23R, RNF114, TNFAIP3, TNIP1, IL4/IL13 and LCE3B/3C [6][7][8][9][10][11] Of these, IL12B and IL23R harbour variants that also confer susceptibility to Crohn's disease (CD) 12 and ankylosing spondylitis. 13 Similarly, TNFAIP3 alleles have been associated with rheumatoid arthritis, 14 systemic lupus erythematosus 15 and type I diabetes. 16 Similar instances of genes conferring susceptibility to multiple conditions (for example, PTPN2, IL2RA and IL2) have emerged from other genome-wide association scans, 17,18 highlighting unexpected connections between clinically distinct disorders.…”

Shared susceptibility variations in autoimmune diseases: a brief perspective on common issues

“…This includes TNFAIP3, where it appears that at least one component of the RA risk is different from the SLE risk haplotype. [17][18][19] The shared risk factors appear to have unique overlaps between different autoimmune diseases. For example, the PTPN22 Arg620Trp that is sheared between several autoimmune diseases including T1DM and RA has been shown not to be a risk factor in MS, whereas in the present studies CD226 and CLEC16A variations are shared risk factors between MS and T1DM.…”