Genetic association between STAT4 and primary Sjögren’s syndrome in Han Chinese women

IntroductionSTAT4, a pivotal transcription factor governing immune and inflammatory responses, has been implicated in autoimmune pathogenesis. This case-control study aimed to examine the relationship between STAT4 single-nucleotide polymorphisms (SNPs) and primary Sjögren’s syndrome (pSS) in a fema...

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Main Authors: Fangfang Li, Junhui Lu, Chao Cen, Wanqiu Zhen, Jiaojiao Zhang, Shengming Wang
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-07-01
Series:Frontiers in Genetics
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Online Access:https://www.frontiersin.org/articles/10.3389/fgene.2025.1628428/full
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author Fangfang Li
Fangfang Li
Junhui Lu
Chao Cen
Wanqiu Zhen
Jiaojiao Zhang
Shengming Wang
Shengming Wang
author_facet Fangfang Li
Fangfang Li
Junhui Lu
Chao Cen
Wanqiu Zhen
Jiaojiao Zhang
Shengming Wang
Shengming Wang
author_sort Fangfang Li
collection DOAJ
description IntroductionSTAT4, a pivotal transcription factor governing immune and inflammatory responses, has been implicated in autoimmune pathogenesis. This case-control study aimed to examine the relationship between STAT4 single-nucleotide polymorphisms (SNPs) and primary Sjögren’s syndrome (pSS) in a female Chinese Han population, exploring potential genetic mechanisms underlying pSS susceptibility.MethodsSix STAT4 single-nucleotide polymorphisms (rs10931481, rs1400656, rs10168266, rs3821236, rs7601754, and rs10174238) were genotyped using MassARRAY, with STAT4 expression determined by quantitative real-time PCR and cytokine levels assessed via ELISA.ResultsThe rs10168266-C allele emerged as a significant risk factor for pSS, with CC homozygotes exhibiting elevated disease susceptibility compared to CT/TT carriers (Pc = 0.001, OR = 1.905). Conversely, the T allele conferred protection (Pc = 0.002, OR = 0.575), and CT genotypes were underrepresented in patients (Pc = 0.003, OR = 0.539). Notably, rs10168266-CC individuals displayed elevated STAT4 expression in peripheral blood mononuclear cells and elevated serum IL-6 levels compared to T allele carriers (both P < 0.05).DiscussionThis study represents the initial investigation to uncover the genetic association between the STAT4 gene and pSS in Han Chinese women. The rs10168266 polymorphism in the STAT4 gene is a novel genetic determinant of pSS susceptibility in female Chinese Han populations. The mechanism may involve dysregulation of IL-6 signaling driven by STAT4, offering a theoretical foundation for the advancement of gene therapy.
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spelling doaj-art-10dd2d7ccc144f74b18d744b1438b0e42025-08-20T02:50:12ZengFrontiers Media S.A.Frontiers in Genetics1664-80212025-07-011610.3389/fgene.2025.16284281628428Genetic association between STAT4 and primary Sjögren’s syndrome in Han Chinese womenFangfang Li0Fangfang Li1Junhui Lu2Chao Cen3Wanqiu Zhen4Jiaojiao Zhang5Shengming Wang6Shengming Wang7The First Clinical College, Chongqing Medical University, Chongqing, ChinaDepartment of Ophthalmology, The Affiliated Huai’an Hospital of Xuzhou Medical University, Huai’an, Jiangsu, ChinaDepartment of Ophthalmology, The Affiliated Huai’an Hospital of Xuzhou Medical University, Huai’an, Jiangsu, ChinaThe First Clinical College, Chongqing Medical University, Chongqing, ChinaThe First Clinical College, Chongqing Medical University, Chongqing, ChinaThe First Clinical College, Chongqing Medical University, Chongqing, ChinaCollege of Stomatology, Chongqing Medical University, Chongqing, ChinaDepartment of Stomatology, The Affiliated Huai’an Hospital of Xuzhou Medical University, Huai’an, Jiangsu, ChinaIntroductionSTAT4, a pivotal transcription factor governing immune and inflammatory responses, has been implicated in autoimmune pathogenesis. This case-control study aimed to examine the relationship between STAT4 single-nucleotide polymorphisms (SNPs) and primary Sjögren’s syndrome (pSS) in a female Chinese Han population, exploring potential genetic mechanisms underlying pSS susceptibility.MethodsSix STAT4 single-nucleotide polymorphisms (rs10931481, rs1400656, rs10168266, rs3821236, rs7601754, and rs10174238) were genotyped using MassARRAY, with STAT4 expression determined by quantitative real-time PCR and cytokine levels assessed via ELISA.ResultsThe rs10168266-C allele emerged as a significant risk factor for pSS, with CC homozygotes exhibiting elevated disease susceptibility compared to CT/TT carriers (Pc = 0.001, OR = 1.905). Conversely, the T allele conferred protection (Pc = 0.002, OR = 0.575), and CT genotypes were underrepresented in patients (Pc = 0.003, OR = 0.539). Notably, rs10168266-CC individuals displayed elevated STAT4 expression in peripheral blood mononuclear cells and elevated serum IL-6 levels compared to T allele carriers (both P < 0.05).DiscussionThis study represents the initial investigation to uncover the genetic association between the STAT4 gene and pSS in Han Chinese women. The rs10168266 polymorphism in the STAT4 gene is a novel genetic determinant of pSS susceptibility in female Chinese Han populations. The mechanism may involve dysregulation of IL-6 signaling driven by STAT4, offering a theoretical foundation for the advancement of gene therapy.https://www.frontiersin.org/articles/10.3389/fgene.2025.1628428/fullgenetic variantssusceptibilityprimary Sjögren’s syndromesingle nucleotide polymorphismSTAT4
spellingShingle Fangfang Li
Fangfang Li
Junhui Lu
Chao Cen
Wanqiu Zhen
Jiaojiao Zhang
Shengming Wang
Shengming Wang
Genetic association between STAT4 and primary Sjögren’s syndrome in Han Chinese women
Frontiers in Genetics
genetic variants
susceptibility
primary Sjögren’s syndrome
single nucleotide polymorphism
STAT4
title Genetic association between STAT4 and primary Sjögren’s syndrome in Han Chinese women
title_full Genetic association between STAT4 and primary Sjögren’s syndrome in Han Chinese women
title_fullStr Genetic association between STAT4 and primary Sjögren’s syndrome in Han Chinese women
title_full_unstemmed Genetic association between STAT4 and primary Sjögren’s syndrome in Han Chinese women
title_short Genetic association between STAT4 and primary Sjögren’s syndrome in Han Chinese women
title_sort genetic association between stat4 and primary sjogren s syndrome in han chinese women
topic genetic variants
susceptibility
primary Sjögren’s syndrome
single nucleotide polymorphism
STAT4
url https://www.frontiersin.org/articles/10.3389/fgene.2025.1628428/full
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