Neutrophil cytosolic factor 2 (NCF2) gene polymorphism is associated with juvenile‐onset systemic lupus erythematosus, but probably not with other autoimmune rheumatic diseases in children

• Published in: Molecular genetics & genomic medicine Vol. 10; no. 1; pp. e1859 - n/a
• Main Authors: Bakutenko, Ivan Y., Haurylchyk, Irena D., Nikitchenko, Natalia V., Sechko, Elena V., Kozyro, Inna A., Tchitchko, Alexei M., Batyan, Galina M., Sukalo, Alexander V., Ryabokon, Nadezhda I.
• Format: Journal Article
• Language: English
• Published: United States John Wiley & Sons, Inc 01.01.2022; John Wiley and Sons Inc; Wiley
• Subjects: Adolescent; Arthritis; Autoimmune diseases; Case-Control Studies; Child; Children; Children & youth; Chronic conditions; Chronic granulomatous disease; Gene polymorphism; Genetic diversity; genetic risk factor; Genotype & phenotype; Genotyping; Hospitals; Humans; Infant, Newborn; Inflammatory diseases; juvenile idiopathic arthritis; juvenile‐onset systemic lupus erythematosus; Kawasaki disease; Leukocytes (neutrophilic); Lupus; Lupus Erythematosus, Systemic - genetics; Microorganisms; Mucocutaneous lymph node syndrome; NAD(P)H oxidase; NADPH Oxidases - genetics; NCF2 gene; Neonates; Neutrophils; Nucleotides; Original; Oxidase; Patients; Phagocytosis; Polymerase chain reaction; Polymorphism; Polymorphism, Single Nucleotide; Population control; Rheumatic diseases; Rheumatic Diseases - genetics; Risk analysis; Risk factors; Single-nucleotide polymorphism; Systemic lupus erythematosus; Kawasaki disease; juvenile idiopathic arthritis; NCF2 gene; juvenile-onset systemic lupus erythematosus; genetic risk factor
• ISSN: 2324-9269; 2324-9269
• DOI: 10.1002/mgg3.1859

Background Genetic variations of neutrophil cytosolic factor 2 (NCF2), a subunit of NADPH oxidase, are usually associated with chronic granulomatous disease, and their relationship with autoimmune disorders through the defective NADPH oxidase function during phagocytosis is suggested. Our study aimed to explore whether there is an association between the non‐synonymous single nucleotide polymorphism in the NCF2 gene (rs17849502, NC_000001.11:g.183563445G>T) and the development of juvenile autoimmune rheumatic diseases. Methods In order to test this hypothesis, we conducted a pilot case–control study. In total, 709 children and adolescents, all Belarusians, were involved in the study including patients with juvenile‐onset systemic lupus erythematosus (JSLE), juvenile idiopathic arthritis (JIA), Kawasaki disease (KD), and subjects without autoimmune and inflammatory diseases as the clinical control, as well as health newborns as the population control. Real‐time polymerase chain reaction was used for genotyping. Results The minor T allele of NCF2 occurred most frequently in patients with JSLE (OR = 2.60, 95% CI = 1.18–5.73, p = 0.023 as compared to the clinical control). In groups with JIA and KD, its frequency did not differ from the control. The TT genotype was only observed in 5.7% of patients with JSLE (p = 0.007), but not in other groups. Conclusion Therefore, our study suggested that NCF2 rs17849502 polymorphism is a potential genetic risk factor for JSLE, while it is probably not for such autoimmune rheumatic diseases as JIA or KD. As far as we know, our study is the first one that identifies the rs17849502 functional polymorphism of the NCF2 gene may be a genetic risk factor of juvenile‐onset systemic lupus erythematosus (JSLE) in the European population. The results of our pilot work also suggest that it is probably not for other autoimmune rheumatic diseases, such as juvenile idiopathic arthritis or Kawasaki disease. These data highlight the importance of NCF2 polymorphism in JSLE pathogenesis and indicate that further research is required in order to prove whether the rs17849502 polymorphism could be recommended for confirming a diagnosis in JSLE patients.