Association between AIRE gene polymorphism and rheumatoid arthritis: a systematic review and meta-analysis of case-control studies

Abstract

Autoimmune regulator (AIRE) is a transcription factor that functions as a novel player in immunological investigations. In the thymus, it has a pivotal role in the negative selection of naive T-cells during central tolerance. Experimental studies have shown that single nucleotide polymorphism (SNP) alters transcription of the AIRE gene. SNPs thereby provide a less efficient negative selection, propagate higher survival of autoimmune T-cells, and elevate susceptibility to autoimmune diseases. To date, only rheumatoid arthritis (RA) has been analysed by epidemiological investigations in relation to SNPs in AIRE. In our meta-analysis, we sought to encompass case-control studies and confirm that the association between SNP occurrence and RA. After robust searches of Embase, PubMed, Cochrane Library, and Web of Science databases, we found 19 articles that included five independent studies. Out of 11 polymorphisms, two (rs2075876, rs760426) were common in the five case-control studies. Thus, we performed a meta-analysis for rs2075876 (7145 cases and 8579 controls) and rs760426 (6696 cases and 8164 controls). Our results prove that rs2075876 and rs760426 are significantly associated with an increased risk of RA in allelic, dominant, recessive, codominant heterozygous, and codominant homozygous genetic models. These findings are primarily based on data from Asian populations.

Chemokine C-C Motif Ligand 4 Gene Polymorphisms Associated with Susceptibility to Rheumatoid Arthritis

“…Single nucleotide polymorphisms (SNPs) denote the single nucleotide variations occurring at specific sites in the genome with appreciable frequency within the population. Genotyping SNPs of a population and comparing the distribution frequency of SNPs among subgroups (e.g., controls and patients) are frequently utilized to examine disease risk and prognosis, including RA [ 9 – 11 ]. For example, the polymorphisms of the chemokine C-C motif ligand 4 (CCL4) gene influence gene expression and protein function and predict risk and prognosis of various diseases, including hepatocellular carcinoma, oral cancer, and psoriasis [ 12 – 14 ].The CCL4 belongs to a cluster of genes located in the chromosomal region 17q11-q21.…”

Analysis of the autoimmune regulator (AIRE) gene variant rs2075876 (G/A) association with breast cancer susceptibility

“…Several AIRE variants were previously shown to be associated with many autoimmune diseases, 13,13,13,13 including rheumatoid arthritis, 18,40 vitiligo, 41 systemic sclerosis, 42 Addison disease, 43 systemic lupus erythematosus, 44 and alopecia areata 25 . However, a limited number of association studies for rs2075876 G>A polymorphism were identified 25,40,45‐47 .…”

“…The human AIRE gene is located in the chromosome 21q22.3 region. Polymorphisms in this gene were previously shown to be genetically associated with autoimmune diseases, such as rheumatoid arthritis and autoimmune polyendocrine syndrome type 1 among others 18,19 . The pathogenic variant rs2075876, caused by a point mutation (c.653‐387G>A) in intron 5 (chr21:44289270), is located within exons forming the domain in the middle of protein chain, which functions in chromatin‐dependent transcriptional regulation, nuclear localization, and oligomer formation 20 …”

The rs878081 polymorphism of AIRE gene increases the risk of rheumatoid arthritis in a Chinese Han population: a case-control study

“…Dysfunction of the AIRE gene could lead to autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy ( 20 , 21 ). The association between several SNPs (rs2075876, rs760426, rs1800250, rs2776377, rs1055311, rs933150, rs1003854, rs2256817, rs374696, rs1078480) of the AIRE gene and RA risk was studied before, and a recent meta-analysis ( 22 ) proved that rs2075876 and rs760426 are significantly associated with an increased risk of RA. After genotype-tissue expression analysis indicated that TT genotype of rs878081 polymorphism significantly decreased the AIRE expression, many researchers focused on the association between AIRE rs878081 polymorphism and RA risk.…”