Evaluation of ACE1 I/D gene polymorphism as a prognostic molecular genetic marker of severity of COVID-19 in juvenile idiopathic arthritis





juvenile idiopathic arthritis, COVID-19, children, ACE1 gene polymorphism


The role of ACE1 I/D gene polymorphism in predicting the severity of COVID-19 (coronavirus infection) in children with autoimmune diseases, including juvenile idiopathic arthritis (JIA), is an important aspect for determining the tactics of personalised therapy. 

Aim - to study the features of the clinical course of COVID-19 and allelic polymorphism of the ACE1 gene in JIA to predict the severity of coronavirus infection.

Materials and methods. The course of COVID-19 was retrospectively analysed in 44 patients with JIA and 20 children without chronic somatic pathology (control group). Genomic DNA preparations were isolated and purified, which made up the Patient Biobank for genotyping at rs4646994 of the ACE1 gene.

Results. In the majority (70.0%) of children with JIA, COVID-19 infection has a mild, subclinical course. Insufficient medication control of JIA activity may be a predicted risk factor for more severe COVID-19. The severity of COVID-19 is not a risk factor for exacerbation of autoimmune disease. In the study of the distribution of ACE I/D genotypes and alleles in children with JIA depending on the severity of COVID-19, no significant difference in the groups was obtained. The DD genotype was significantly more common in the group of children with mild COVID-19 without rheumatological pathology and there was a tendency to increase the frequency of the genotype (II insertion) among patients with JIA who had mild COVID-19 compared with the control group.

Conclusions. In the mild course of COVID-19 in patients with JIA, the DI genotype at the ACE1 rs4646994 gene was significantly more frequent and there is a tendency to increase the frequency of the genotype (II insertion). Such genotypes in patients with JIA may lead to an imbalance of the components of the renin-angiotensin system, but, on the other hand, they can be considered as protective, due to which the group of children with JIA does not develop severe COVID-19.

The research was carried out in accordance with the principles of the Declaration of Helsinki. The study protocol was approved by the Local Ethics Committees of the institutions indicated in the work. Informed consent of the child and child's parents was obtained for the research.

No conflict of interest was declared by the authors.


Brodin P. (2022). SARS-CoV-2 infections in children: Understanding diverse outcomes. Immunity. 55(2): 201-209. https://doi.org/10.1016/j.immuni.2022.01.014; PMid:35093190 PMCid:PMC8769938

Cotugno N, Amodio D, Buonsenso D et al. (2023). Susceptibility of SARS-CoV2 infection in children. Eur J Pediatr. 182: 4851-4857. https://doi.org/10.1007/s00431-023-05184-w; PMid:37702769 PMCid:PMC10640404

Cristiani L, Mancino E, Matera L et al. (2020). Will children reveal their secret? The coronavirus dilemma. Eur Respir J. 55(4): 2000749. https://doi.org/10.1183/13993003.00749-2020; PMid:32241833 PMCid:PMC7113798

Cui X, Zhao Z, Zhang T et al. (2021). A systematic review and meta-analysis of children with coronavirus disease 2019 (COVID-19). J Med Virol. 93(2): 1057-1069. https://doi.org/10.1002/jmv.26398; PMid:32761898 PMCid:PMC7436402

Dioguardi M, Cazzolla AP, Arena C et al. (2021). Innate Immunity in Children and the Role of ACE2 Expression in SARS-CoV-2 Infection. Pediatr Rep. 13(3): 363-382. Published 2021 Jul 2. https://doi.org/10.3390/pediatric13030045; PMid:34287338 PMCid:PMC8293341

Ehrenfeld M, Tincani A, Andreoli L, Cattalini M, Greenbaum A, Kanduc D et al. (2020, Aug). Covid-19 and autoimmunity. Autoimmunity Review. 19(8): 102597. https://doi.org/10.1016/j.autrev.2020.102597; PMid:32535093 PMCid:PMC7289100

Ishak A, Mehendale M, Al Rawashdeh MM et al. (2022). The association of COVID-19 severity and susceptibility and genetic risk factors: A systematic review of the literature. Gene. 836: 146674. https://doi.org/10.1016/j.gene.2022.146674; PMid:35714803 PMCid:PMC9195407

Keikha M, Karbalaei M. (2022). Global distribution of ACE1 (rs4646994) and ACE2 (rs2285666) polymorphisms associated with COVID-19: A systematic review and meta-analysis. Microb Pathog. 172: 105781. https://doi.org/10.1016/j.micpath.2022.105781; PMid:36116608 PMCid:PMC9476369

Lai CC, Liu YH, Wang CY et al. (2020). Asymptomatic carrier state, acute respiratory disease, and pneumonia due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2): Facts and myths. J Microbiol Immunol Infect. 53(3): 404-412. https://doi.org/10.1016/j.jmii.2020.02.012; PMid:32173241 PMCid:PMC7128959

Livshits LA, Harashchenko TA, Umanets TR et al. (2021). Relationship between the Prevalence of ACE1 I/D Polymorphism Genotype II and Covid-19 Morbidity, Mortality in Ukraine and in Some Europe Countries. Journal Cytology and Genetics. 55(5): 427-432. https://doi.org/10.3103/S0095452721050054; PMid:34565928 PMCid:PMC8450713

Long X, Zhu J, Zhao R et al. (2020). Epidemiology and clinical features of highly pathogenic human coronavirus infection in children. Chin J Pediatr. 58(5): E014.

Marushko TV. (2018). Yuvenilnyi idiopatychnyi artryt. Zdorovia Ukrainy. Tematychnyi nomer «Pediatriia». 1(44): 39-41.

Ministry of Health of Ukraine. (2022). Orhanizatsiia nadannia medychnoi dopomohy khvorym na koronavirusnu khvorobu (COVID-19). Nakaz MOZ Ukrainy vid 28.03.2020 No. 722. URL: https://moz.gov.ua/uploads/3/19713-standarti_med_dopomogi_covid_19.pdf

Ochani R, Asad A, Yasmin F et al. (2021). COVID-19 pandemic: from origins to outcomes. A comprehensive review of viral pathogenesis, clinical manifestations, diagnostic evaluation, and management. Infez Med. 29(1): 20-36.

Onel KB, Horton DB, Lovell DJ, Shenoi S, Cuello CA, Angeles-Han ST et al. (2022). 2021 American College of Rheumatology Guideline for the Treatment of Juvenile Idiopathic Arthritis: Recommendations for Nonpharmacologic Therapies, Medication Monitoring, Immunizations, and Imaging. Arthritis care & research. 74(4): 505-520. https://doi.org/10.1002/acr.24839; PMid:35233989 PMCid:PMC10231687

Rifai N, Alwakeel H, Shaaban H, Abdelfattah M. (2018). Angiotensin-converting enzyme polymorphism and pediatric pneumonia. Egyptian Pediatric Association Gazette. 66(4): 121-124. https://doi.org/10.1016/j.epag.2018.08.001

Schurink B, Roos E, Vos W, Breur M, van der Valk P, Bugiani M. ACE2 Protein Expression During Childhood, Adolescence, and Early Adulthood. Pediatr Dev Pathol. 2022;25(4):404-408. https://doi.org/10.1177/10935266221075312; PMid:35220822 PMCid:PMC9277324

WHO. (2023). Coronavirus Disease (COVID-19) Situation Reports. Geneva: World Health Organization. URL: https://www.who.int/news-room/fact-sheets/detail/coronavirus-disease-(covid-19).





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