Juvenile idiopathic arthritis is associated to a functionally active polymorphism in the SH2D2A gene

Objective

T cell specific adapter protein (TSAd) is involved in the negative control of T cell activation. The SH2D2A gene encoding TSAd is located on chromosome 1q21 which has been implicated in susceptibility to experimental autoimmune disorders in the mouse (chronic allergic encephalomyelitis and collagen-induced arthritis). Recently we found that short alleles of the SH2D2A gene promoter are associated with multiple sclerosis (MS). The aim of our study was to investigate whether the SH2D2A promoter polymorphism contributes to the genetic susceptibility to develop juvenile idiopathic arthritis (JIA).

Methods

DNA from 212 Norwegian patients with juvenile arthritis (categorized as systemic (n = 18), poly- RF+ (n = 12), poly- RF- (n = 61), oligo- (n = 87) and extended oligoarthritis (n = 31)) and 279 healthy unrelated Norwegian controls were genotyped for a functional GA repeat polymorphism in the promoter region of SH2D2A gene using an ABI automatic sequencing machine (ABI PrismTM XL377)

Results

The frequencies of the two shortest alleles GA13 and GA16 were increased among the JIA patients compared to the control; the GA13 significantly so (0.098 vs 0.053, OR=1,97, P = 0,0063). When we divided patients into subgroups only in the RF-positive polyarthritis group of patients there was no increases of any of the short alleles. All other subgroups of JIA showed an increased frequency of GA13, however only in the patients with oligoarthritis the increased frequency of GA13 allele reached significance (0.103, P = 0.017). When we analyzed the frequency of short alleles in relation to the occurrence of chronic iridiocyclitis (CIC) in the group of patients with oligoarthritis (n = 14), we found that 57% of the these patients carry at least one short allele compared to 46% of the patients without CIC (n = 73).

Conclusion

Our data indicate that the short alleles of the SH2D2A promoter associated with JIA patients could contribute to the genetic susceptibility of JIA, similar what we have observed in MS. It is possible that the short allele is a marker for particular clinical presentations. This we will investigate in further details.