Association between STAT4 polymorphisms and risk of primary biliary cholangitis: a meta-analysis

Abstract

Primary biliary cholangitis (PBC) is a chronic autoimmune liver disease. Several studies reported that SATA4 (signal transducer and activator of transcription 4) polymorphisms were significantly associated with PBC susceptibility. In order to derive a more comprehensive estimation of the association between STAT4 and PBC risk, this meta-analysis was conducted. Thirteen eligible studies from 8 articles with a total number of 11,310 cases and 27,844 controls were included in this meta-analysis. Pooled odds ratios (OR) and 95% confidence intervals (CI) were estimated with fixed effects model or random effects model. The results showed statistically significant association between polymorphisms of rs7574865, rs3024921, rs6752770, rs7601754 and rs10168266 in STAT4 and PBC risk under the allelic effect model (rs7574865, T vs. G, OR = 1.24, 95% CI 1.14-1.35; rs3024921, T vs. A, OR = 1.65, 95% CI 1.44-1.91; rs6752770, G vs. A, OR = 1.24, 95% CI 1.11-1.39; rs7601754, A vs. G, OR = 1.35, 95% CI 1.17-1.55; and rs10168266, T vs. C, OR = 1.31, 95% CI 1.22-1.41). Furthermore, the rs7574865 polymorphism was significantly associated with PBC risk under all genotype genetic models (dominant effect model: TT + TG vs. GG, OR = 1.43, 95% CI 1.19-1.71; recessive effect: TT vs. TG + GG, OR = 1.40, 95% CI 1.24-1.58; and co-dominant effect: TT vs. GG, OR = 1.67, 95% CI 1.37-2.02). The sensitivity analysis by omitting one study at a time showed that the results were stable. No publication bias was indicated from both Begg's test and Egger's weighted regression. This meta-analysis suggested that polymorphisms of rs7574865, rs3024921, rs6752770, rs7601754 and rs10168266 in STAT4 were significantly associated with the risk of PBC.

Influence of STAT4 Genetic Variants and Serum Levels on Multiple Sclerosis Occurrence in the Lithuanian Population

“…It was also noticed that the rs7574865 T allele was statistically significantly associated with susceptibility to SS in the Spanish population (OR = 1.61; 95% CI: 1.29-1.99; p < 0.001) [25]. According to a study carried out by Zhang et al, the results showed a statistically significant association between the STAT4 rs7601754 A allele and the risk of primary biliary cholangitis (OR = 1.35; 95% CI: 1.17-1.55; p < 0.001) [37]. Although various sources indicate associations of STAT4 rs10181656, rs7574865, rs7601754, and rs10168266 with inflammatory and autoimmune diseases, in our study, only rs7601754 was statistically significantly associated with the occurrence of MS.…”

Identification of genetic biomarkers for alloimmunization in sickle cell disease

“…STAT4 encodes the transcription factor signal transducer and activator of transcription 4, which is involved in IL12‐mediated T‐helper cell type 1 (Th1) and IL23‐mediated Th17 responses (Thierfelder et al , ; Neurath, ). This specific variant has been associated with chronic autoimmune liver disease (Zhang et al , ) and other STAT4 variants have been associated with various antibody‐mediated autoimmune diseases such as Systemic lupus erythematosus, Rheumatoid arthritis and Type 1 Diabetes (Remmers et al , ; Korman et al , ; Lee et al , ; Rueda et al , ).…”