Polymorphisms in IRF5 and TYK2 Genes Are Associated with Rheumatoid Arthritis in a Chinese Han Population

Abstract

Background The IRF5 and TYK2 gene polymorphisms are associated with autoimmune diseases. However, the relationship between the IRF5 and TYK2 gene polymorphisms and RA risk in the Chinese Han population was inconsistent. Material/Methods A total of 578 RA patients (case group) and 578 healthy controls (control group) were assessed in a case-control study. Genotyping of IRF5 (Exon 6 insertion/deletion (in/de), rs2004640, rs2070197, rs10954213) and TYK2 (rs280500, rs280519, rs280521, rs8108236, rs12720253) was performed by direct sequencing method. Data analysis was performed by SHEsis. Results The rs2004640T allele ( P =0.0003) and the dominant ( P =0.001) and recessive ( P =0.01) models of rs2004640 were associated with RA risk after stringent Bonferroni correction (0.05/4). The IRF5 exon 6 (in), rs2070197 and rs10954213 were not associated with RA ( P >0.05). Two haplotypes of IRF5 (DTAT and DTGG) were associated with RA susceptibility ( P <0.05). In addition, the frequencies of TYK2 rs280500A, rs280521A, and rs8108236A were significantly higher in the RA group compared with the control group ( P <0.05). TYK2 rs280500, rs280521, and rs8108236 were associated with RA susceptibility in the dominant model, but the same was not observed for rs280519 and rs12720253 ( P <0.05). Furthermore, 3 risk haplotypes (AAAGT, AGGAT, and GAAAT) and a protective haplotype (GAGGT) of TYK2 gene were associated with RA susceptibility ( P <0.05). Conclusions Our results suggest that IRF5 rs2004640, TYK2 rs280500, rs280521, rs8108236, and haplotypes IRF5 (DTAT and DTGG) and TYK2 (AAAGT, AGGAT, GAAAT, and GAGGT) are susceptible factors for RA in a Chinese Han population.

Associations of genetic variants within TYK2 with pulmonary tuberculosis among Chinese population

“…Peng et al. discovered that a series of SNPs in TYK2 including rs280500, rs280521, and rs8108236 were associated with rheumatoid arthritis among Chinese population (Peng et al., 2021) and verified that TYK2 gene makes functional roles in the physiological and pathological processes of some diseases. Another study on peripheral blood mononuclear cells revealed that the SNP rs280520 in TYK2 was associated with increased IFN‐gamma production (van de Schoor et al., 2022).…”

Genetic association between the PTPN22, IRF5 and TYK2 gene variants and susceptibility to juvenile idiopathic arthritis

“…The IRF5 gene contains nine exons and is located on the human genome 7q32 (48). Studies have shown that loci in IRF5, including exon 6(de/in), rs2004640, rs10954213, rs2280714 and rs2070197 are important susceptibility factors for autoimmune diseases (21)(22)(23). The IRF5 rs2004640T allele creates a 5'-donor splicing site in intron 1, resulting in the expression of untranslated exon 1B (49).…”

“…In addition, tyrosine kinase 2 (TYK2), a member of the receptor tyrosine kinase Janus kinase (JAK) family, has been shown to serve an important role in the type I IFN signaling pathway (20). Furthermore, IRF5 and TYK2 genes variants are suggested to be related to the susceptibility of autoimmune diseases including SLE, RA and multiple sclerosis (MS) (21)(22)(23). However, few studies on the genetic association between the IRF5 and TYK2 gene variants and JIA susceptibility have been reported.…”

Progress and application on severe combined immunodeficiency mouse model for rheumatoid arthritis: a literature review

“…Previous studies 2,3 have shown that it may be related to immune cells, autoantigens, and cytokines, and it is related to the intestinal flora. Some studies have reported that it may be related to genetic polymorphisms 4,5 . At present, the number of cases is increasing year by year, and the number of female patients is significantly higher than that of male patients 6 .…”