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Gene. 2019 Jun 20;702:8-16. doi: 10.1016/j.gene.2019.03.033. Epub 2019 Mar 20.

Genetic implications in the pathogenesis of rheumatoid arthritis; an updated review.

Author information

1
Rheumatology Research Center, Tehran University of Medical Sciences, Tehran, Iran; Department of Immunology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran.
2
Rheumatology Research Center, Tehran University of Medical Sciences, Tehran, Iran.
3
Department of Medical Genetics, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran.
4
Rheumatology Research Center, Tehran University of Medical Sciences, Tehran, Iran. Electronic address: mahmoudim@tums.ac.ir.

Abstract

Three important factors, including genetics, environment factors and autoimmunity play a role in the pathogenesis of rheumatoid arthritis (RA). The heritability of RA has been accounted to be 50-60%, while the HLA involvement in heritability of the disease has been accounted to be 10-40%. It has been documented that shared epitope (SE) alleles, such as HLA-DRB1*01 and DRB1*04, some HLA alleles like HLA-DRB1*13 and DRB1*15 are connected to RA susceptibility. An advanced classification of SE categorizes SE alleles into four main groups namely, S1, S2, S3D, and S3P. The S2 and S3P groups have been linked to susceptibility of seropositive RA. Various genome-wide association studies (GWAS) have discovered many susceptibility loci implicated in pathogenesis of RA. Some of the important single nucleotide polymorphisms (SNPs) linked to RA are TRAF1, STAT4, CTLA4, IRF5, CCR6, PTPN22, IL23R, and PADI4. HLA and non-HLA genes may discriminate anti-cyclic citrullinated peptide (anti-CCP) antibody-positive and anti-CCP-negative RA groups. Furthermore, risk of the disease has also been linked to environmental agents, mainly cigarette smoking. Pharmacogenomics has also confirmed SNPs or genetic patterns that might be linked to drugs responses. Different aspects of genetic involvement in the pathogenesis, etiology, and RA complications are reviewed in this article.

KEYWORDS:

Genetics; HLA shared epitope; Pathogenesis; Rheumatoid arthritis

PMID:
30904715
DOI:
10.1016/j.gene.2019.03.033
[Indexed for MEDLINE]

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