Polymorphisms of the STAT4 gene in the pathogenesis of tuberculosis.

Shouquan Wu,Yu Wang,Jian-Qing He,Miaomiao Zhang,Minggui Wang

doi:10.1042/bsr20180498

Shouquan Wu, Yu Wang + Show 3 more

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https://doi.org/10.1042/bsr20180498

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Journal: Bioscience reports	Publication Date: Aug 29, 2018
Citations: 5	License type: CC BY 4.0

Affiliation: Sichuan University

Abstract

The signal transducer and activator of transcription 4 (STAT4) gene encodes a transcription factor that transmits signals induced by several cytokines which play critical roles in the development of autoimmune and chronic inflammatory diseases. In the present study, we have investigated the association between STAT4 polymorphisms and a predisposition to Mycobacterium tuberculosis (MTB) infection and pulmonary tuberculosis (PTB). In the present study, a total of 209 cases of PTB, 201 subjects with latent TB infection (LTBI), and 204 healthy controls (HC) were included. Logistic regression analyses were used to calculate P-values, odds ratios (ORs), and 95% confidence intervals (CIs) for assessing the association between single nucleotide polymorphisms (SNPs) and disease risk. We used Bonferroni correction to adjust the P-values. Genotyping was conducted using the improved multiplex ligase detection reaction (iMLDR) method. For the rs7574865 polymorphism, the GT genotype is less frequent in the LTBI group compared with HC (P=0.028, OR = 0.62; 95%CI: 0.40–0.95). In addition, the prevalence of the rs897200 CC genotype was lower in the PTB cases compared with LTBI individuals (P=0.039, OR = 0.54; 95%CI: 0.30–0.97). However, no SNPs within STAT4 were associated with PTB or LTBI after Bonferroni correction. Our study demonstrated that STAT4 variants were not related to LTBI and PTB.

Highlights

Tuberculosis (TB) continues to be a leading cause of morbidity and mortality in low-income and middle-income countries
Studies have demonstrated that the specific strain of Mycobacterium tuberculosis (MTB), environmental factors, and host genetics could explain why the incidence of TB is different amongst particular races, geographic areas, genders, and age groups [4,5]
signal transducer and activator of transcription 4 (STAT4) polymorphisms have been associated with various diseases, e.g. STAT4 rs8179673 was demonstrated to be a protective factor against hepatitis B virus (HBV) infection [24]. rs7582694 has been associated with immune-related diseases such as multiple sclerosis [25], systemic lupus erythematosus [25], and type-1 autoimmune hepatitis [26]

Summary

Introduction

Tuberculosis (TB) continues to be a leading cause of morbidity and mortality in low-income and middle-income countries. Recent epidemiologic data demonstrated that approximately 1.7 billion people are infected with Mycobacterium tuberculosis (MTB) [2]. Only 5–15% of infected individuals will develop TB during their lifetime [3]. It remains unknown why only a minority of infected subjects progress to active disease. Studies have demonstrated that the specific strain of MTB, environmental factors, and host genetics could explain why the incidence of TB is different amongst particular races, geographic areas, genders, and age groups [4,5]. Evidence from twin studies indicated that host genetics is involved in the progression of TB [6] and estimates of the heritable component of TB vary from 39 to 71% [7,8]

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