Association between FAS gene -670 A/G and -1377 G/A polymorphisms and the risk of autoimmune diseases: a meta-analysis.

Hongwei Yan,Yuxiao Hong,Yunfei Cai

doi:10.1042/bsr20191197

Hongwei Yan, Yuxiao Hong + Show 1 more

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https://doi.org/10.1042/bsr20191197

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Abstract

Objectives: FAS plays a critical role in the extrinsic apoptosis pathway in autoimmune diseases. Previous studies investigating the association between FAS gene −670 A/G and −1377 G/A polymorphisms and the risk of autoimmune diseases reported controversial results. We performed the meta-analysis to evaluate the possible association. Methods: Relevant studies were identified by searching the PubMed, Embase, CNKI, and Wanfang databases up to December 2018. Odds ratios (ORs) and corresponding 95% confidence intervals (CIs) were calculated to determine the association. Results: A total of 43 articles including 67 studies (52 studies for FAS −670 A/G and 15 studies for −1377 G/A) were included in the meta-analysis. Our meta-analysis showed that the FAS −670 A/G polymorphism was associated with the risk of autoimmune diseases (GG vs. GA: OR = 1.079, 95% CI = 1.004–1.160, P=0.038), especially in Caucasians (GG vs. GA: OR = 1.12, 95% CI = 1.03–1.23, P=0.012), Asians (G vs. A: OR = 0.89, 95% CI = 0.83–0.96, P=0.002), systemic lupus erythematosus (SLE) (G vs. A: OR = 0.85, 95% CI = 0.77–0.94, P=0.001), multiple sclerosis (MS) (GG+GA vs. AA: OR = 0.83, 95% CI = 0.70–0.99, P=0.043), systemic sclerosis (SSc) (GG vs. GA: OR = 1.20, 95% CI = 1.07–1.36, P=0.003) and Hashimoto’s thyroiditis (HT) (G vs. A: OR = 1.45, 95% CI = 1.10–1.90, P=0.008); the FAS −1377 G/A polymorphism was associated with the risk of autoimmune diseases (A vs. G: OR = 1.11, 95% CI = 1.03–1.20, P=0.008), especially in Asians (A vs. G: OR = 1.15, 95% CI = 1.05–1.25, P=0.002) and high quality studies (A vs. G: OR = 1.14, 95% CI = 1.05–1.24, P=0.002). Conclusion: This meta-analysis demonstrated that the FAS –670A/G and –1377 G/A polymorphisms were associated with the risk of autoimmune diseases.

Highlights

Autoimmune diseases are chronic disorders characterized by the loss of immune tolerance to self-antigens, leading to immune-mediated tissue destruction
In the FAS −670 A/G polymorphism, a significant association between FAS −670 A/G and the risk of autoimmune diseases was observed under the heterozygous genetic model (GG vs. GA: odds ratio (OR) = 1.079, 95% confidence interval (CI) 1.004–1.160, P=0.038)
In the FAS −1377 G/A polymorphism, our results indicated that FAS −1377 G/A polymorphism was associated with the risk of autoimmune diseases (A vs. G: OR = 1.11, 95% CI = 1.03–1.20, P=0.008; AA vs. GG: OR = 1.23, 95% CI = 1.03–1.47, P=0.024; AA+AG vs. GG: OR = 1.14, 95% CI = 1.02–1.26, P=0.015)

Summary

Introduction

Autoimmune diseases are chronic disorders characterized by the loss of immune tolerance to self-antigens, leading to immune-mediated tissue destruction. They affect 4–5% of adults, the majority of whom are women [1]. FAS ( known as APO-1, CD95, or TNFSF6) is a cell surface receptor that belongs to the tumor necrosis factor (TNF) receptor superfamily [13]. FAS is widely expressed in normal human tissues. To maintain self-tolerance, the binding of FAS-ligand (FASL) to FAS on the cell surface initiates the extrinsic apoptosis pathway [14]; autoreactive lymphocytes are normally eliminated. Abnormal apoptosis may lead to a failure to eliminate autoreactive lymphocytes, which can induce the appearance

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