Association of NCF2, NCF4, and CYBA Gene Polymorphisms with Rheumatoid Arthritis in a Chinese Population

Abstract

Objective. Recent studies have focused on the special roles of NADPH-oxidase in multiple autoimmune diseases. Nevertheless, the association of genetic variation in NADPH-oxidase genes with rheumatoid arthritis (RA) was not extensively studied in a Chinese population. We performed this study to examine the association of NCF2, NCF4, and CYBA gene polymorphisms with RA susceptibility in a Chinese population. Methods. Six single nucleotide polymorphisms (SNPs) (NCF2 rs10911363, NCF4 rs1883112, rs4821544, rs729749, CYBA rs3794624, and rs4673) were genotyped in a cohort composed of 593 RA patients and 596 normal controls. Improved multiple ligase detection reaction (iMLDR) was used for genotyping. Results. We observed that NCF4 rs4821544 CT genotype and C allele frequencies in RA patients were significantly decreased when compared to controls (CT vs. TT: P = 0.043 ; C vs. T: P = 0.031 ), and rs4821544 polymorphism was significantly associated with an increased RA risk under the dominant model (TT vs. CT+CC: P = 0.031 ). Our results also indicated that rs729749 CT genotype frequency was significantly lower in RA patients than that in controls (CT vs. CC: P = 0.033 ). Moreover, the rs729749 CT genotype frequency was also significantly decreased in RA patients in males (CT vs. CC: P = 0.024 ). No significant association between NCF2 and CYBA gene polymorphisms and RA susceptibility was observed. There were significant associations between rs4821544 TT genotype and T allele frequencies and anti-CCP in male RA patients. Conclusions. In summary, NCF4 rs4821544 and rs729749 polymorphisms might contribute to RA susceptibility, while NCF2 and CYBA gene polymorphisms were not associated with RA susceptibility.

NCF4 dependent intracellular reactive oxygen species regulate plasma cell formation

“…Nevertheless, a copy number variation in NCF1 has been found associated with RA [ 11 ]. In addition, it was also found that SNPs linked to the NCF4 gene was associated with RA [ 13 , 14 ]. These findings confirm previous discoveries in animal models, where Ncf1 was found to be major gene controlling both arthritis [ 15 , 16 ] and lupus [ 17 ].…”

One year in review 2021: pathogenesis of rheumatoid arthritis

“…Among these, NCF4 has been proven to regulate the production of intracellular ROS by inducing the NOX complex to phagosome membranes through the binding of phosphatidylinositol 3-phos-phate. In this regard, Zhang TP et al demonstrated that gene polymorphisms of NCF4 rs4821544 and rs729749, but not of NCF2 and CYBA, contribute to RA susceptibility (12). In parallel to gene polymorphisms, epigenetic mechanisms, including DNA methylation, histone modifications, and small (s) and long (l) non-coding RNAs (ncRNA) play important roles in mechanisms underlying RA pathogenesis.…”

NCF4 regulates antigen presentation of cysteine peptides by intracellular oxidative response and restricts activation of autoreactive and arthritogenic T cells

“…A neutrophil cytosolic factor 1 ( NCF1 ) polymorphic allele, which causes a low reactive oxygen response, has been shown to be a causative factor in SLE and possibly also in RA [ [2] , [3] , [4] ]. Associations between RA and single nucleotide polymorphisms (SNP) in the NCF4 gene have also been identified [ 2 , 5 ]. Both NCF1 and NCF4 are components of the NADPH oxidase type 2 (NOX2) complex, which is known to be responsible for the induced production of reactive oxygen species (ROS) [ 6 ].…”