Evaluation of HLA-G 14 bp Ins/Del and +3142G>C Polymorphism with Susceptibility and Early Disease Activity in Rheumatoid Arthritis

Abstract

Purpose/Background. Mounting evidence designates that HLA-G plays a role in the regulation of inflammatory processes and autoimmune diseases. There are controversial reports concerning the impact of HLA-G gene polymorphism on rheumatoid arthritis (RA). This study was aimed at examining the impact of 14 bp ins/del and +3142G>C polymorphism with susceptibility and early disease activity in RA patients in a sample of the Iranian population. Methods. This case-control study was done on 194 patients with RA and 158 healthy subjects. The HLA-G rs1063320 (+3142G>C) and rs66554220 (14 bp ins/del) variants were genotype by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFP) and PCR method, respectively. Results. The HLA-G +3142G>C polymorphism significantly decreased the risk of RA in codominant (OR = 0.61, 95% CI = 0.38–0.97, p = 0.038, GC versus GG; OR = 0.36, 95% CI = 0.14–0.92, p = 0.034, CC versus GG), dominant (OR = 0.56, 95% CI = 0.36–0.87, p = 0.011, GC + CC versus GG), and allele (OR = 0.58, 95% CI = 0.41–0.84, p = 0.004, C versus G) inheritance models tested. Our finding did not support an association between HLA-G 14 bp ins/del variant and risk/protection of RA. In addition, no significant association was found between the polymorphism and early disease activity. Conclusion. In summary, our results showed that HLA-G +3142G>C gene polymorphism significantly decreased the risk of RA in a sample of the Iranian population.

HLA‐G: Function, polymorphisms and pathology

“…In a recent analysis carried out in 140 RA patients and 125 control subjects, a lack of association between HLA-G14 bp INS/DEL variants and risk/protection of RA was reported (Gautam et al, 2019). In addition, the HLA-G +3142G>C polymorphism was found to be associated with a decreased risk of RA as attributed to recessive inheritance tested model results (Hashemi et al, 2016).…”

Genetic association between HLA-G 14-bp polymorphism and diseases: A systematic review and meta-analysis

“…Articles included comprised case-control studies involving the HLA-G 3′UTR 14-bp polymorphism and clinical situations/ diseases. Studies were grouped according to clinical characteristics, pathogenesis and immune response as follow: (1) cancer 2 -B-Cell Lymphoma [27], Breast Cancer [28][29][30][31][32], Cervical Cancer [33][34][35][36], Colorectal cancer [37], Esophageal Cancer [38], Hepatocellular Carcinoma [39][40][41], Head and Neck Squamous-Cell Carcinoma (HNSCC) [42], Lung Cancer [43], Neuroblastoma [44], Papillary Thyroid Cancer [45] and Prostate Cancer [46]; (2) autoimmune diseases 3 -Hashimoto's Thyroiditis [45], Juvenile Idiopathic Arthritis [47], Multiple Sclerosis [48][49][50][51], Non-segmental Vitiligo [52], Pemphigus Vulgaris [53], Rheumatoid Arthritis [47,[54][55][56][57][58], Systemic Lupus Erythematosus (LES) [59][60][61][62][63][64][65][66][67] and Type 1 Diabetes [68]…”

Genetics and rheumatoid arthritis susceptibility in Iran

“…The HLA-G gene encodes seven HLA-G bound and soluble isoforms, including HLA-G1, -G2, -G3, and -G4 proteins; sHLA-G5; sHLA-G6; and sHLA-G7. The HLA-G gene has limited individual tissue expression in nonpathological situations and may inhibit immunoregulatory functions of CD4+ and CD8+ lymphocytes, and cytotoxic activity of dendritic and natural killer (NK) cells (Hashemi et al, 2016). The 14-bp deletion allele was shown to be more frequent in the juvenile form of RA, but not the adult form, and demonstrated no association with clinical manifestations or disease severity.…”

“…Furthermore, the 14-bp ins/ins genotype was related to the enhanced production of sHLA-G and an improved therapeutic response to methotrexate in adult patients with RA (Veit et al, 2008). Hashemi et al (2016) evaluated the association of the HLA-G 14 bp ins/del and +3142G>C polymorphism with susceptibility and early disease activity in RA in the Iranian population. They found no relationship between the HLA-G 14 bp ins/del variant and risk for RA in the Iranian population.…”