We concluded that STAT4rs7574865 is associated with SLE susceptibility in the Iranian population and this SNP might be a factor in the pathogenesis of SLE.
In a combined analysis of 1596 SLE patients and 2540 controls for selected 22 candidate SNP, STAT4 and BLK as positive controls showed a strong association with SLE (FDR p=9.85×10(-13) and 2.28×10(-8), respectively).
Furthermore, the stratified meta-analysis also demonstrate that the STAT4rs7574865 polymorphism is associated with the presence of autoantibodies with systemic reactivity (anti-ds-DNA antibodies) in SLE patients (OR = 1.37; 95% CI = 1.21 - 1.56, P = 1.12 × 10(-6)).
Meta-analysis followed by replication identifies loci in or near CDKN1B, TET3, CD80, DRAM1, and ARID5B as associated with systemic lupus erythematosus in Asians.
Meta-analysis followed by replication identifies loci in or near CDKN1B, TET3, CD80, DRAM1, and ARID5B as associated with systemic lupus erythematosus in Asians.
The genomic regions bound by the transcription complexes mediated by IRF5 and STAT4 were examined for transcription factor binding motifs and SLE-associated sequence variants.
Our studies confirmed an association of the STAT4 C (rs7582694) variant with the development of SLE and occurrence of some clinical manifestations of the disease.
This meta-analysis demonstrates that the STAT4rs7574865 T allele confers susceptibility to SLE, RA, T1D, SSc, JIA, APS, IBD-UC, and pSS patients, supporting the hypothesis of association between STAT4 gene polymorphism and subgroup of autoimmune diseases.
Further, we confirmed the genetic association between lupus and 5 additional lupus susceptibility loci (ITGAM, MSH5, CFB, STAT4, and FCGR2A; P = 7.5 × 10⁻¹¹, P = 5.2 × 10⁻⁸, P = 8.7 × 10⁻⁷ , P = 0.0058, and P = 0.0070, respectively), and provided evidence, for the first time, of genome-wide significance for the association between lupus in African American patients and ITGAM and MSH5 (HLA region).
For example, rs7574865 in STAT4 had an OR for anti-dsDNA + SLE of 1.77 (95% CI 1.57-1.99, p = 2.0E-20) compared to an OR for anti-dsDNA - SLE of 1.26 (95% CI 1.12-1.41, p = 2.4E-04), with p(heterogeneity)<0.0005.
The results of our study demonstrated that STAT4rs7582694 SNP was significantly associated with SLE, and these results were in accordance with previous studies.
STAT1 was also associated with SLE in this cohort (P(meta)=3.3 × 10⁻⁵), but this association signal appears to be dependent of that previously reported for the neighbouring STAT4 gene.
We decided to investigate the association of single-nucleotide polymorphisms (SNPs) in the IRF7/KIAA1542 region (rs4963128, rs2246614, and rs702966) and in STAT4 (rs7574865 and rs7582694) with SLE disease in a Northern Han Chinese population of 748 patients and 750 healthy controls.
With these studies, it has been established that a number of genes associated with SLE in Caucasians are also risk factors in Asians: HLA class II genes, STAT4, BANK1, BLK, IRF5, TNFSF4, ITGAM, etc., while there are also novel genetic risk factors identified by these studies in Asians, for instance, the ETS1 and WDFY4 in Chinese.