Rs2004640

From SNPedia

rs2004640, a SNP in the IRF5 gene in chromosomal region 7q32.1, is one of several SNPs associated with systemic lupus erythematosus (SLE). This association has been observed in multiple populations (Caucasian, Asian, and African-Americans).

The association was first noted in two relatively large studies of Caucasian patients.[PMID 15657875, PMID 16642019]

In ~600 Korean SLE patients, the odds ratio for the rs2004640(T) risk allele was 1.44 (CI: 1.34-1.55, overall p=1.85x10e-23). The rs2004640-T/rs2280714-T haplotype involved in both the alternative splice donor site and the elevated expression of the IRF5 protein also had a highly significant association with SLE (pooled p=2.11x 10e-16).[PMID 17389033]

[PMID 18288123] Reconfirmed for African-Americans

[PMID 17166181] Reconfirmed in ~370 female Caucasian patients

[PMID 17189288] Reconfirmed in ~380 UK SLE families

[PMID 18311811] Pooled data from two populations (Japanese and Korean) were combined to determine that the rs2004640(T) allele frequency was significantly increased in SLE patients (p = 8.3 x 10^-5).

[PMID 18063667] A variant located 64 bp upstream of the first untranslated exon (exon 1A), consisting of a 5 bp insertion/deletion CGGGG, may be the causative SNP in this region that is most responsible for increasing SLE risk, however it lacks an rs# (i.e. it isn't registered in dbSNP).

[PMID 18843785] In a Korean population, rs2004640 was associated with both the anti-CCP Ab-positive (odds ratio 1.47, CI: 1.15-1.88, pcorr = 0.01) and SE-positive group (odds ratio 1.54, CI: 1.14-2.09, pcorr = 0.03) forms of rheumatoid arthritis. Combined analysis pooling 3 independent cohorts yielded an association with an odds ratio of 1.21, CI: 1.07-1.38, pooled p = 0.0031 in a dominant model.

[PMID 19116937] rs2004640(T;T) is associated with susceptibility to systemic sclerosis in a study of ~800 French Caucasian patients, with an odds ratio of 1.58 (CI: 1.18 - 2.11, p trend 0.002).

[PMID 19228650] A meta-analysis comprising 5 case-control studies, totaling 6,582 rheumatoid arthritis cases and 5,375 controls, concluded that several IRF5 gene SNPs were indeed (still) significantly associated with the disease. The rs2004640(G) allele was associated with a slight protective effect (odds ratio 0.9, CI: 0.85-0.96, p = 0.002).

[PMID 19479858] Of 3 IRF5 SNPs studied, the rs2280714(A) SNP (and not this one) had the strongest association (odds ratio 1.42, CI: 1.15-1.75) in Japanese SLE patients.

[PMID 19644887] STAT4 is a genetic risk factor for systemic sclerosis having additive effects with IRF5 on disease susceptibility and related pulmonary fibrosis

[PMID 19644876] Association of STAT4 and BLK, but not BANK1 or IRF5, with primary antiphospholipid syndrome

[PMID 19877059] BANK1 is a genetic risk factor for diffuse cutaneous systemic sclerosis and has additive effects with IRF5 and STAT4