Exploration of the association between the single-nucleotide polymorphism of co-stimulatory system and rheumatoid arthritis

Ding-Ping Chen; Ying-Hao Wen; Wei-Tzu Lin; Fang-Ping Hsu; Kuang-Hui Yu

doi:10.3389/fimmu.2023.1123832

Exploration of the association between the single-nucleotide polymorphism of co-stimulatory system and rheumatoid arthritis

Front Immunol. 2023 Jun 29:14:1123832. doi: 10.3389/fimmu.2023.1123832. eCollection 2023.

Authors

Ding-Ping Chen^{1

2}, Ying-Hao Wen^{1

3

4

5}, Wei-Tzu Lin¹, Fang-Ping Hsu¹, Kuang-Hui Yu⁶

Affiliations

¹ Department of Laboratory Medicine, Linkou Chang Gung Memorial Hospital, Taoyuan, Taiwan.
² Department of Medical Biotechnology and Laboratory Science, College of Medicine, Chang Gung University, Taoyuan, Taiwan.
³ School of Medicine, National Tsing Hua University, Hsinchu, Taiwan.
⁴ School of Medicine, Chang Gung University, Taoyuan, Taiwan.
⁵ Graduate Institute of Clinical Medical Sciences, College of Medicine, Chang Gung University, Taoyuan, Taiwan.
⁶ Division of Rheumatology, Allergy, and Immunology, Linkou Chang Gung University and Memorial Hospital, Taoyuan, Taiwan.

Abstract

Introduction: The human leukocyte antigen (HLA) has been linked to the majority of autoimmune diseases (ADs). However, non-HLA genes may be risk factors for ADs. A number of genes encoding proteins involved in regulating T-cell and B-cell function have been identified as rheumatoid arthritis (RA) susceptibility genes.

Methods: In this study, we investigated the association between RA and single-nucleotide polymorphisms (SNPs) of co-stimulatory or co-inhibitory molecules in 124 RA cases and 100 healthy controls without immune-related diseases [including tumor necrosis factor superfamily member 4 (TNFSF4), CD28, cytotoxic T-lymphocyte-associated protein 4 (CTLA4), and programmed cell death protein 1 (PDCD1)].

Results: The results showed that there were 13 SNPs associated with RA, including rs181758110 of TNFSF4 (CC vs. CT, p = 0.038); rs3181096 of CD28 (TT vs. CC + CT, p = 0.035; CC vs. TT, p = 0.047); rs11571315 (TT vs. CT, p = 0.045), rs733618 (CC vs. TT + CT, p = 0.043), rs4553808 (AA vs. AG vs. GG, p = 0.035), rs11571316 (GG vs. AG vs. AA, p = 0.048; GG vs. AG + AA, p = 0.026; GG vs. AG, p = 0.014), rs16840252 (CC vs. CT vs. TT, p = 0.007; CC vs. CT, p = 0.011), rs5742909 (CC vs. CT vs. TT, p = 0.040), and rs11571319 of CTLA4 (GG vs. AG vs. AA, p < 0.001; GG vs. AG + AA, p = 0.048; AA vs. GG + AG, p = 0.001; GG vs. AA, p = 0.008; GG vs. AG, p ≤ 0.001); and rs10204525 (TT vs. CT + CC, p = 0.024; TT vs. CT, p = 0.021), rs2227982 (AA vs. GG, p = 0.047), rs36084323 (TT vs. CT vs. CC, p = 0.022; TT vs. CT + CC, p = 0.013; CC vs. TT + CT, p = 0.048; TT vs. CC, p = 0.008), and rs5839828 of PDCD1 (DEL vs. DEL/G vs. GG, p = 0.014; DEL vs. DEL/G + GG, p = 0.014; GG vs. DEL + DEL/G, p = 0.025; DEL vs. GG, p = 0.007).

Discussion: Consequently, these SNPs may play an important role in immune regulation, and further research into the role of these SNPs of immune regulatory genes in the pathogenesis of RA is required.

Keywords: association; autoimmune disease (AD); co-stimulatory system; rheumatoid arthritis (RA); single nucleotide polymorphism (SNP).

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Arthritis, Rheumatoid* / genetics
CD28 Antigens / genetics
CTLA-4 Antigen / genetics
Genetic Predisposition to Disease
Humans
OX40 Ligand / genetics
Polymorphism, Single Nucleotide*
Tumor Necrosis Factor-alpha / genetics

Substances

CTLA-4 Antigen
CD28 Antigens
Tumor Necrosis Factor-alpha
TNFSF4 protein, human
OX40 Ligand

Grants and funding

This study was supported by grants to D-PC from the Ministry of Science and Technology (110-2320-B-182A-007) and Chang Gung Memorial Hospital (CMRPG3N0021). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.