STAT4 (Phospho-Tyr693) ELISA Kit

Autoimmune diseases (AIDs) are complex diseases characterized by persistent or recurrent inflammation, alteration of immune response, and production of specific autoantibodies. It is known that different AIDs share several susceptibility genetic loci. Tumor necrosis factor alpha inducible protein 3 (TNFAIP3) encodes the ubiquitin-modifying enzyme A20, which downregulates inflammation by restricting NF-kappa B, a transcription factor that regulates expression of various proinflammatory genes. Variants in TNFAIP3 gene have been described as associated with susceptibility to several AIDs. Here, we analyzed two TNFAIP3 polymorphisms in Italian patients with systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), and primary Sjogren's syndrome (pSS), to verify if the genetic variability of TNFAIP3 gene is involved in genetic predisposition to AIDs also in the Italian population. We recruited 313 SLE patients, 256 RA patients, 195 pSS patients, and 236 healthy controls. Genotyping of rs2230926 and rs6920220 in TNFAIP3 gene was performed by an allelic discrimination assay. We carried out a case/control association study and a genotype/phenotype correlation analysis. A higher risk to develop SLE was observed for rs2230926 (P=0.02, OR=1.92). No association was observed between this SNP and the susceptibility to pSS or RA. However, the rs2230926 variant allele seems to confer a higher risk to develop lymphoma in pSS patients, while in RA patients, the presence of RF resulted significantly associated with the variant allele. Regarding the rs6920220 SNP, we observed a significant association of the variant allele with SLE (P=0.03, OR=1.53), pSS (P=0.016, OR=1.69), and RA (P=0.0001, OR=2.35) susceptibility. Furthermore, SLE patients carrying the variant allele showed a higher risk to develop pericarditis, pleurisy, and kidney complications. Our results support the importance of the TNFAIP3 gene variant role in the development of different autoimmune diseases in the Italian population and furtherly confirm a sharing of genetic predisposing factors among these three pathologies.

The objectives of this study were to identify genomic regions by Bayesian methods (BayesA, BayesB, or BayesN) that fit fixed-length haplotypes or SNPs using GenSeL Covariates for haplotype alleles of five lengths (125, 250, 500 kb, 1 or 2 Mb) were generated, and rare haplotypes were removed at three thresholds (1, 5, or 10%). Subsequently, we performed gene network analyses to investigate the biological processes shared by genes that were identified for the same across traits. Genotypes at 41,034 SNPs that were common on OvineSNP5U panel were phased for 751 Scottish Blackface (SBF) lambs. This is the first study to quantify the proportion of genetic variance using haplotypes across the whole genome in an SBF population. The genetic variance explained of ha plotype-based GWAS was higher than that of SNP-based (WAS in across traits studied. In this population, fitting 500kb haplotypes with a I% frequency threshold resulted in the highest proportion of genetic variance explained for nematode resistance and fitting 2Mb haplotypes with a 10% frequency threshold improved genetic variance explained for body weight comparable to fitting SNPs by Bayes13. Candidate genes, including CXCR4, STAT4, CCL1, CCL2, CCL3, CCL5, CCL8, CCL16, CCL18, CARMIL2, and HSPA14 were identified for nematode resistance and ADH5, PPP3CA, and FARP4 for body weight traits. Network analysis provided annotation results linking to all identified candidate genes. This study supported previous results from GWAS of nematode resistance and body weight and revealed additional regions in the ovine genome associated with these economically important traits. These results suggest that network analysis can provide new information regarding biological mechanisms and genes leading to complex phenotypes, like nematode resistance and body weight of lamb.