Association of a single nucleotide polymorphism in theSH2D1Aintronic region with systemic lupus erythematosus

Abstract

SH2D1A, also known as signaling lymphocytic activation molecule (SLAM)-associated protein (SAP), is an adaptor protein. Recently, it was reported that SAP deficient mice were protected from systemic lupus erythematosus (SLE). In this study, we postulated SH2D1A gene to be a candidate susceptibility gene for SLE and analyzed its association with SLE. A case-control association study was conducted on 5 tag single nucleotide polymorphisms (SNPs) in SH2D1A region in 506 Japanese female SLE patients and 330 healthy female controls. The luciferase assay was performed to determine the functional role of the SNP associated with SLE. One SNP in the intron 2, rs2049995, showed association with SLE (p=0.0110, odds ratio (OR) 1.97, 95% confidence interval (CI) 1.16-3.34, under the dominant model). The association of rs2049995 seemed to be stronger in the subset with the age of onset less than 20 years (p=0.0067, OR 2.65, 95% CI 1.28-5.46). Functional evaluation of rs2049995 showed that reporter gene activity was increased 1.9-fold for the susceptible allele compared with the resistant allele. An intronic SNP of SH2D1A is associated with SLE.

A review of signaling and transcriptional control in T follicular helper cell differentiation

“…200,213 It is likely that genetic susceptibility to lupus manifests through alterations to the epigenetic code of Tfh. Disease-associated polymorphisms in noncoding regions associated with many of the pathways we have discussed are enriched in lupus and include SNPs in the loci of OX40, 185 STAT4, 185 SAP, 214 IL-2, and IL-21. 186 Likewise, there are lupus SNPs in the CD40L locus, a necessary Tfh protein for providing optimal "help" to GC B cells.…”

Modelling clinical systemic lupus erythematosus: similarities, differences and success stories

“…This region has a human syntenic equivalent on chromosome 1, 1q21–44, which has been associated with SLE in human linkage studies [31–33]. Human gene associations include Cr2 [34, 35], FcγRIIA , FcγRIIIA and FcγRIIIb [36–38], PARP [39] and CRP / SAP [40, 41]. SLAM family members Ly108 and CD84 have been identified as disease causative in mice, but they may be less significant in human SLE [29, 42].…”

Human Leukocyte Antigens and Systemic Lupus Erythematosus: A Protective Role for the HLA-DR6 Alleles DRB1*13:02 and *14:03

“…It is a systemic inflammatory disease susceptibility to which is associated with genetic and environmental factors [1]. Genetic risk factors for SLE include alleles in IRF5, STAT4, BLK, TNFAIP3, TNIP1, FCGR2B and others [2], [3], [4]; the functional role of the polymorphisms as well as the relationships with other autoimmune diseases such as rheumatoid arthritis were suggested[5], [6]. Especially, altered frequencies of human leukocyte antigen ( HLA ) alleles are known to be associated with SLE.…”