AB0023 ASSOCIATION OF NCF2, NCF4 AND CYBA GENES POLYMORPHISMS WITH RHEUMATOID ARTHRITIS IN A CHINESE POPULATION
Authors: T. P. Zhang, Q. Huang, H. F. Pan, D. Q. Ye, X. Li
Journal: Annals of the Rheumatic Diseases (2020)

Background: Recent studies have focused on the special roles of NADPH-oxidase, which is composed of gp91phox, p22phox, p47phox, p67phox, p40phox encoded by CYBB , CYBA , NCF1 , NCF2 , NCF4 genes, in multiple autoimmune diseases. Nevertheless, the association of genetic variation in NADPH-oxidase genes with rheumatoid arthritis (RA) was not extensively studied in Chinese population. Objectives: We performed this study to examine the association of NCF2 , NCF4 , CYBA genes polymorphisms with RA susceptibility in a Chinese population. Methods: Six single nucleotide polymorphisms (SNPs) ( NCF2 rs10911363, NCF4 rs1883112, rs4821544, rs729749, CYBA rs3794624, rs4673) were genotyped in a cohort composed of 593 RA patients and 596 normal controls. All patients were consecutively enrolled from the Department of Rheumatology at the First Affiliated Hospital of University of Science and Technology of China and the First Affiliated Hospital of Anhui Medical University, and the normal controls was enrolled from the same region. Improved multiple ligase detection reaction (iMLDR) was used for genotyping. Chi-square ( χ 2 ) test was used to analyze the association of the genotype and allele frequencies of above SNPs and RA. Odds ratios ( OR ) and 95% confidence interval ( CI ) were also evaluated using Logistic regression analyses, and haplotype analysis was assessed using SHEsis software. Results: There were 101 males and 492 females in RA group with a mean age of 51.59±6.68 years, and the normal control group included 97 males and 499 females with an average age of 52.32±12.63 years. We observed that NCF4 rs4821544 CT genotype, 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). Moreover, 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). No significant association between NCF2 , CYBA genes polymorphisms and RA susceptibility was observed. There were no significant differences in allele, genotype frequencies of above SNPs between RA patients with RF-positive and with RF-negative, as well as anti-CCP-positive RA patients and anti-CCP-negative RA patients. Conclusion: In summary, NCF4 rs4821544, rs729749 polymorphisms might contribute to RA susceptibility, while NCF2 , CYBA genes polymorphisms were not associated with RA susceptibility. References: [1]Nauseef WM. Assembly of the phagocyte NADPH oxidase, Histochem Cell Biol, 2004;122:277-291. [2]Groemping Y, Rittinger K. Activation and assembly of the NADPH oxidase: a structural perspective, Biochem J (2005) 386:401-416. [3]Olsson LM, Nerstedt A, Lindqvist AK, Johansson SC, Medstrand P, Olofsson P, et al. Copy Number Variation of the Gene NCF1 Is Associated with Rheumatoid Arthritis, Antioxid Redox Signal(2012)16:71-78.DOI:10.1089/ars.2011.4013 Table 1. Genotype and allele frequencies of NCF2, NCF4, CYBA genes polymorphisms in RA patients and controls [n(%)] SNP Analyze model RA (N = 593) Control (N = 596) P value NCF2 rs10911363 Genetypes GG 125 144 0.371 GT 304 289 0.747 TT 164 163 Alleles G 554 577 0.408 T 632 615 NCF4 rs1883112 Genetypes GG 57 56 0.972 GA 248 255 0.754 AA 288 285 Alleles G 362 367 0.888 A 824 825 rs4821544 Genetypes CC 4 7 0.323 CT 117 146 0.043 TT 472 443 Alleles C 125 160 0.031 T 1061 1032 Dominant model TT 472 443 0.031 CT+CC 121 153 rs729749 Genetypes TT 104 102 0.445 CT 266 302 0.033 CC 223 192 Alleles T 474 506 0.219 C 712 686 CYBA rs3794624 Genetypes AA 14 15 0.929 GA 160 147 0.368 GG 419 43 Alleles A 188 177 0.498 G 998 1015 rs4673 Genetypes AA 1 5 0.140 GA 85 90 0.673 GG 507 501 Alleles A 87 100 0.34 G 1099 1092 Acknowledgments: no Disclosure of Interests: None declared