Comprehensive assessment of the association between genes on JAK-STAT pathway (IFIH1, TYK2, IL-10) and systemic lupus erythematosus: a meta-analysis

Previous studies have reported that genes relating to JAK-STAT pathway (IFIH1, TYK2 and IL-10) conferred the susceptibility to SLE. In this study, we performed a meta-analysis (including 43 studies) to evaluate the association between IFIH1 (9288 patients and 24,040 controls), TYK2 (4928 patients and 11,536 controls), IL-10 (3623 patients and 4907 controls) polymorphisms and systemic lupus erythematosus (SLE) in a comprehensive way. We found that IFIH1 rs1990760_T allele was associated with risk of SLE in overall population under three models (allelic: P = 2.56 × 10−11, OR 1.135, 95% CI 1.094–1.179, dominant: P = 1.8 × 10−8, OR 1.203, 95% CI 1.128–1.284, recessive: P = 2.6 × 10−7, OR 1.163, 95% CI 1.098–1.231). A strong association had been observed between TYK2 polymorphism rs2304256_C allele and SLE in Europeans (P = 5.82 × 10−5, OR 1.434, 95% CI 1.203–1.710). When coming to overall population, TYK2 rs2304256_C showed a significant association with SLE under recessive model (P = 8.05 × 10−3, OR 1.314, 95% CI 1.074–1.608). However, the other two SNPs (rs12720270, rs280519) of TYK2 were not significant. The results also indicated an association between IL-10 rs1800896_G allele and SLE in Asians under recessive model (P = 4.65 × 10−3, OR 2.623, 95% CI 1.346–5.115), while, IL-10 rs1800896_G had a trend of association with SLE in European population in dominant model (P = 1.21 × 10−2, OR 1.375, 95% CI 1.072–1.764). In addition, we found IL-10 rs1800896 GG homozygote might be associated with increased susceptibility to SLE (GG vs AA, P = 4.65 × 10−3, OR 1.539, 95% CI 1.142–2.072). We concluded that IFIH1 rs1990760_T and TYK2 rs2304256_C alleles were significantly associated with SLE, and IL-10 rs1800896 GG homozygote might have an enhancement effect on SLE risk.