STAT4 is a Genetic Risk Factor for Systemic Sclerosis in a Chinese Population

Abstract

Systemic sclerosis (SSc) is an immune-mediated and complex genetic disease. An association of single-nucleotide polymorphisms (SNPs) in the STAT4 gene with SSc has been reported in European Caucasians, North Americans and Japanese. We undertook the current study to examine whether the STAT4 SNPs are also associated with susceptibility to SSc and SSc subsets in a Han Chinese population. A total of 453 Han Chinese patients with SSc and 534 healthy controls were examined in the study. The SNPs rs7574865, rs10168266 and rs3821236 of the STAT4 gene were examined with SNP TaqMan assays. The T-allele carriers of rs7574865 and rs10168266 were strongly associated with the presence of anti-topoisomerase I (ATA) and pulmonary fibrosis in SSc patients, as well as with diffuse cutaneous SSc (dcSSc). The presence of anti-centromere (ACA) and limited cutaneous SSc (lcSSc) did not show significant association with any of the examined SNPs. The results were consistent with previous reports in other ethnic populations in supporting the notion that polymorphisms of STAT4 may play an important role in susceptibility to SSc. It also revealed different genetic aspects of SSc subsets in a Han Chinese population.

Polymorphisms in STAT4 and IRF5 increase the risk of systemic sclerosis: a meta‐analysis

“…For STAT4 rs7574865 polymorphism, four studies, including 2853 cases and 5228 controls, were screened . For IRF5 rs2004640 polymorphism, three studies, including 1893 cases and 2171 controls, were contained .…”

“…For STAT4 rs7574865 polymorphism, four studies, including 2853 cases and 5228 controls, were screened. [24][25][26][27] For IRF5 rs2004640 polymorphism, three studies, including 1893 cases and 2171 controls, were contained. [27][28][29] The major characteristics of eligible publications are reported in Table 1, and genotype frequencies are listed in Table 2.…”

Association of Signal Transducer and Activator of Transcription 4 rs10181656 Polymorphism With Rheumatoid Arthritis and Systemic Sclerosis in Khuzestan Province in Southwestern Iran

“…9 Third intron of the STAT4 encompasses a few polymorphisms (rs18889341, rs7574865, rs8179673, and rs10181656) which have been reported to be associated with RA and SSc in some populations worldwide. [21][22][23][24][25] However, this association remains to be challenging based on some studies conducted on the Southwestern Chinese Han, Turkish, African American and Southwestern Iran populations. [26][27][28] Persistent and strong association between the STAT4 polymorphisms and RA and SSc in multiple independent and different ethnic populations suggested 25 an important role of STAT4 gene in pathogenesis of SSc and RA in European and Asian populations and is considered a risk factor for both diseases.…”

Genetic implications in the pathogenesis of systemic sclerosis

“…In 2 SSc GWASs containing White European populations, STAT4 showed genome‐wide significance threshold . Hence, STAT4 can be characterized as a risk factor for SSc and in particular for fibrosis in internal organs . Actually, STAT4 gene rs7574865 polymorphisms showed a new SSc genetic risk factor, which can be associated with SSc.…”