Taken together, these data provide support for the existence of a locus at or near SLC11A1 that is a strong susceptibility factor for JIA in Finnish patients.
We identified two susceptibility loci for JIA, AFF3 and the IL2/IL21 region and additional weak evidence supporting an association with the CTLA4 and IL7R genes, which warrant further investigation.
Variants originally associated with juvenile idiopathic arthritis (VTCN1 gene), sarcoidosis (ANXA11 gene), primary biliary cirrhosis (IL12RB2 gene) and celiac disease (LPP gene) were not associated with type 1 diabetes in our dataset.
There were statistically significant differences in frequencies of genotype and allele in CD14C-159T polymorphism between JIA group and control group (genotype: chi-squared = 33.168, p < 0.05, CT vs CC, OR 2.946, 95% CI 1.739-4.990; TT vs CC, OR 5.426, 95% CI 2.977-9.891.
In the present study, we investigated whether alleles at D6S265, or other markers in this region, also modify the risk for JIA on other haplotypes, i.e., DRB1*1301-DQB1*0603 or DRB1*1101/4-DQB1*0301.
We found DRB1*0801/DQB1*0402 haplotype to be strongly associated (p < 0.001) with JIA, supporting findings of the haplotype associations-based ASP design.
Also, a non-significant increase in the frequency of the DRB1*04, *11 and *15 alleles was detected in the polyarticular subtype of the Kuwaiti JRA cases compared to the controls.
Besides PTPN22, STAT4 and PTPN2 variants, IL2, IL2RA, IL2RB, as well as IL6 and IL6R loci also harbor variants associated with oligoarticular and RF-negative polyarticular JIA.
Our results confirm that certain HLA-DRB1 alleles reported previously as susceptibility factors are strongly associated with JIA in a Hungarian population.
This meta-analysis confirms that the PTPN221858 C/T polymorphism is associated with JIA susceptibility in Europeans and shows that the MIF -173 C/G polymorphism may be associated with susceptibility to JIA.
PTPN22rs2476601 is associated with JIA and numerous other autoimmune diseases, and has been reported to show female-specific association with type 1 diabetes.