Genetic Polymorphism of Ficolin-2 in Arctic Populations

Aim. To study the prevalence of polymorphisms rs17549193 and rs7851696 of the ficolin-2 gene FCN2 among the Nenets, Dolgan-Nganasan and Slavic populations using a molecular genetic study of single nucleotide polymorphisms.

Design. Comparative population-genetic research.

Materials and methods. Newborn infants of the Taimyr Dolgan-Nenets district of the Krasnoyarsk Territory — Nenets (n = 261) and Dolgan-Nganasan (n = 104) — and Slavic children of Krasnoyarsk aged 8–18 years with and without bronchial asthma of varying severity were examined. DNA extraction from venous blood and dry blood stains was performed. The genotyping of polymorphisms rs17549193 and rs7851696 of the FCN2 gene was performed by real-time polymerase chain reaction.

Results. The minor allele of the polymorphism rs17549193 FCN2 in Nenets is significantly less than in Slavs of control group and with asthma — 19.9% vs. 28.8% (p < 0.001) and 27.5% (p = 0.002). The prevalence of the T allelic variant rs7851696 FCN2 in the Nenets and Dolgan-Nganasans is also lower than in the Slavs with and without asthma — 7.3 and 3.8% vs. 14.6 and 12.6% (p < 0.05).

Conclusion. Due to the fact that most human diseases are genetic determinism, it is relevant to study the characteristic features in individual populations to draw up recommendations to healthcare organizations. Understanding the role and functions of ficolin-2 as one of the proteins of the lectin pathway of activation of the complement system is of great importance for the development of new methods of disease prevention and evaluation of the functioning of immune protection.

1. Rantanen M., Karpechko A.Yu., Lipponen A., Nordling K. et al. The Arctic has warmed nearly four times faster than the globe since 1979. Commun. Earth Environ. 2022;3:168. DOI: 10.1038/s43247-022-00498-3

2. Semenza J.C., Paz S. Climate change and infectious disease in Europe: impact, projection and adaptation. Lancet Regional Health — Europe. 2021;9:100230. DOI: 10.1016/j.lanepe.2021.100230

3. Nikanov A.N., Dorofeev V.M., Talykova L.V., Sturlis N.V. et al. Morbidity of adult population in the Russian European Arctic with intensive mining and metallurgical industry. Russian Arctic. 2019;1(6):20–7. (in Russian). DOI: 10.24411/2658-4255-2019-10063

4. Andersson A.M., Halling A.S., Loft N., Skov L. et al. Atopic dermatitis among children and adolescents in the Arctic region — a systematic review and meta-analysis. J. Eur. Acad. Dermatol. Venereol. 2021;35(8):1642–54. DOI: 10.1111/jdv.17276

5. Petrova D.P., Mindlina A.Ya. Comparative analysis of the morbidity of respiratory infections in the Arctic Zone and other territories of Russia. Epidemiology and Vaccinal Prevention. 2020;19(4):48–56. (in Russian). DOI: 10.31631/2073-3046-2020-19-4-48-56

6. Balashova S.N., Samodova A.V., Dobrodeeva L.K., Belisheva N.K. Hematological reactions in the inhabitants of the Arctic on a polar night and a polar day. Immun. Inflamm. Dis. 2020;8(3):415–22. DOI: 10.1002/iid3.323

7. Malyavskaya S.I., Lebedev A.V., Kostrova G.N., Torshin I.Yu. et al. Associations between pathogenetic factors of metabolic and circulatory syndromes in young adults in a Russian Arctic city. Human Ecology. 2021;28(2):47–56. (in Russian). DOI: 10.33396/1728-0869-2021-2-47-56

8. Kabbani M.S., Shchegoleva L.S. Adaptive immune response in residents of the Russian Arctic zone and South Ossetia. IOP Conf. Ser: Earth Environ. Sci. 2019;302:012076. DOI: 10.1088/1755-1315/302/1/012076

9. Conigliaro P., Triggianese P., Ballanti E., Perricone C. et al. Complement, infection, and autoimmunity. Curr. Opin. Rheumatol. 2019;31(5):532–41. DOI: 10.1097/BOR.0000000000000633

10. Smolnikova M.V., Tereshchenko S.Yu. Proteins of the lectin pathway of the complement system activation: immunobiological functions, genetics and involvement in the pathogenesis of human diseases. Russian Journal of Infection and Immunity. 2022;12(2):209–21. (in Russian). DOI: 10.15789/2220-7619-POT-1777

11. Garlatti V., Belloy N., Martin L., Lacroix M. et al. Structural insights into the innate immune recognition specificities of L- and H-ficolins. EMBO J. 2007;26(2):623–33. DOI: 10.1038/sj.emboj.7601500

12. Pan Q., Chen H., Wang F., Jeza V.T. et al. L-ficolin binds to the glycoproteins hemagglutinin and neuraminidase and inhibits influenza A virus infection both in vitro and in vivo. J. Innate Immun. 2012;4(3):312–24. DOI: 10.1159/000335670

13. Aoyagi Y., Adderson E.E., Rubens C.E., Bohnsack J.F. et al. L-ficolin/ mannose-binding lectin-associated serine protease complexes bind to group B Streptococci primarily through N-acetylneuraminic acid of capsular polysaccharide and activate the complement pathway. Infection and Immunity. 2008;76(1):179–88. DOI: 10.1128/IAI.00837-07

14. Gil E., Noursadeghi M., Brown J.S. Streptococcus pneumoniae interactions with the complement system. Front. Cell Infect. Microbiol. 2022;12:929483. DOI: 10.3389/fcimb.2022.929483

15. Świerzko A.S., Jarych D., Gajek G., Chojnacka K. et al. Polymorphisms of the FCN2 gene 3’UTR region and their clinical associations in preterm newborns. Front. Immunol. 2021;12:741140. DOI: 10.3389/fimmu.2021.741140

16. Metzger M.L., Michelfelder I., Goldacker S., Melkaoui K. et al. Low ficolin-2 levels in common variable immunodeficiency patients with bronchiectasis. Clin. Exp. Immunol. 2015;179(2):256–64. DOI: 10.1111/cei.12459

17. Garred P., Honoré C., Ma Y.J., Rørvig S. et al. The genetics of ficolins. JIN. 2010;2(1):3–16. DOI: 10.1159/000242419

18. Jensen M.L., Honoré C., Hummelshøj T., Hansen B.E. et al. Ficolin-2 recognizes DNA and participates in the clearance of dying host cells. Mol. Immunol. 2007;44(5):856–65. DOI: 10.1016/j.molimm.2006.04.002

19. Badarukhiya J.A., Tupperwar N., Nizamuddin S., Mulpur A.K. et al. Novel FCN2 variants and haplotypes are associated with rheumatic heart disease. DNA Cell Biol. 2021;40(10):1338–48. DOI: 10.1089/dna.2021.0478

20. Hummelshoj T., Munthe-Fog L., Madsen H.O., Fujita T. et al. Polymorphisms in the FCN2 gene determine serum variation and function of ficolin-2. Hum. Mol. Genet. 2005;14(12):1651–8. DOI: 10.1093/hmg/ddi173

21. Giang N.T., Tong H.V., Nghia T.H., Hung H.V. et al. Association of FCN2 polymorphisms and ficolin-2 levels with dengue fever in Vietnamese patients. Int. J. Infect. Dis. 2020;95:253–61. DOI: 10.1016/j.ijid.2020.02.029

22. Xu D.D., Wang C., Jiang F., Wei L.L. et al. Association of the FCN2 gene single nucleotide polymorphisms with susceptibility to pulmonary tuberculosis. PLoS One. 2015;10(9):e0138356. DOI: 10.1371/journal.pone.0138356

23. Smolnikova M.V., Tereshchenko S.Yu. Lectin pathway proteins deficiency of the complement system activation in the Arctic population. Immunologiya. 2023;44(4):455–62. (in Russian). DOI: 10.33029/0206-4952-2023-44-4-455-462

24. Haerynck F., Van Steen K., Cattaert T., Loeys B. et al. Polymorphisms in the lectin pathway genes as a possible cause of early chronic Pseudomonas aeruginosa colonization in cystic fibrosis patients. Hum. Immunol. 2012;73(11):1175–83. DOI: 10.1016/j.humimm.2012.08.010

25. van Kempen G., Meijvis S., Endeman H., Vlaminckx B. et al. Mannose-binding lectin and l-ficolin polymorphisms in patients with community-acquired pneumonia caused by intracellular pathogens. Immunology. 2017;151(1):81–8. DOI: 10.1111/imm.12705

26. Elkoumi M.A., Emam A.A., Allah M.A.N., Sherif A.H. et al. Association of ficolin-2 gene polymorphisms and susceptibility to systemic lupus erythematosus in Egyptian children and adolescents: a multicenter study. Lupus. 2019;28(8):995–1002. DOI: 10.1177/0961203319856089