Ассоциация полиморфизма rs11362 гена DEFB1 с предрасположенностью к тяжелой бронхиальной астме

Mualliflar

  • Сатликов Р.К Заведующий кафедрой ВПТ,гематологии и диагностики Ургенчского государственного медицинского института, кандидат медицинских наук ##default.groups.name.author##
  • Абдуллаев Р.Б Заведующий кафедрой внутренних болезней, нефрологии, гемодиализа и реабилитации Ургенчского государственного медицинского института, доктор медицинских наук, профессор ##default.groups.name.author##
  • Зиядуллаев Ш.Х заместитель директора по учебной работе Самаркандского филиала Ташкентского международного университета, доктор медицинских наук, профессор ##default.groups.name.author##
  • Каримов Х.Р Невролог, заведующий отделением реабилитации и физиотерапии Ургенчского районного медицинского объединения Хорезмской области ##default.groups.name.author##

Kalit so‘zlar:

DEFB1, rs11362, тяжелая бронхиальная астма, врожденный иммунитет, бета-дефензин

Abstrak

Актуальность: бета-дефензин-1 человека, кодируемый геном DEFB1, является ключевым антимикробным пептидом эпителия дыхательных путей, и полиморфизм rs11362 может влиять на его экспрессию и вносить вклад в предрасположенность к тяжелой бронхиальной астме. Ранее эта ассоциация не изучалась среди населения Центральной Азии. Методы: в данном исследовании типа «случай-контроль» геномная ДНК была выделена из периферической венозной крови 70 взрослых узбекских пациентов с тяжелой бронхиальной астмой и 30 здоровых узбекских лиц контрольной группы из Хорезмской области

##plugins.themes.default.displayStats.downloads##

##plugins.themes.default.displayStats.noStats##

Havolalar

1. Chen Y, Han Z, Zhang S, Liu H, Wang K, Liu J, Liu F, Yu S, Sai N, Mai H, Zhou X, Zhou C, Wen Q, Ma L. ERK1/2-CEBPB axis-regulated hBD1 enhances anti-tuberculosis capacity in alveolar type II epithelial cells. Int J Mol Sci. 2024;25(4):2408. doi:10.3390/ijms25042408

2. Nagib M, Sayed AM, Korany AH, Abdelkader K, Shari FH, Mackay WG, Rateb ME. Human defensins: structure, function, and potential as therapeutic antimicrobial agents with highlights against SARS CoV-2. Probiotics Antimicrob Proteins. 2025;17:1563-83. doi:10.1007/s12602-024-10436-8

3. Othumpangat S, Noti JD. beta-Defensin-1 regulates influenza virus infection in human bronchial epithelial cells through the STAT3 signaling pathway. Pathogens. 2023;12(1):123. doi:10.3390/pathogens12010123

4. Wozniak W, Sechet E, Kwon YJ, Aulner N, Navarro L, Sperandio B. Identification of human host factors required for beta-defensin-2 expression in intestinal epithelial cells upon a bacterial challenge. Sci Rep. 2024;14:15442. doi:10.1038/s41598-024-66568-y

5. Slebioda Z, Wozniak T, Dorocka-Bobkowska B, Wozniewicz M, Kowalska A. Beta-defensin 1 gene polymorphisms in the pathologies of the oral cavity—data from meta-analysis: association only with rs1047031 not with rs1800972, rs1799946, and rs11362. J Oral Pathol Med. 2021;50(1):22-31. doi:10.1111/jop.13136

6. Cane J, Tregidgo L, Thulborn S, Finch D, Bafadhel M. Antimicrobial peptides SLPI and beta defensin-1 in sputum are negatively correlated with FEV1. Int J Chron Obstruct Pulmon Dis. 2021;16:1437-47. doi:10.2147/COPD.S301622

7. Farag AGA, Shoeib MAA, Labeeb AZ, Sleem AS, Khallaf HMA, Khalifa AS, et al. Human beta-defensin 1 circulating level and gene polymorphism in non-segmental vitiligo Egyptian patients. An Bras Dermatol. 2023;98(2):181-8. doi:10.1016/j.abd.2022.04.002

8. Emulina DE, Abola I, Brinkmane A, Isakovs A, Skadins I, Moisejevs G, et al. The impact of IL1B rs1143634 and DEFB1 rs11362 variants on periodontitis risk in phenylketonuria and type 1 diabetes mellitus patients in a Latvian population. Diagnostics (Basel). 2024;14(2):192. doi:10.3390/diagnostics14020192

9. Fernandez-Torres J, Zamudio-Cuevas Y, Martinez-Flores K. Polymorphic variation of the DEFB1 gene might contribute to the development of ankylosing spondylitis: a preliminary study. Mol Biol Rep. 2024;51(1):1051. doi:10.1007/s11033-024-09985-6

10. Vargas-Alarcon G, Perez-Mendez O, Martinez-Rios MA, Diaz-Santillan I, Morales-Villamil LA, Delgadillo-Rodriguez H, Posadas-Sanchez R, Ramirez-Bello J, Fragoso JM. The DEFB1 gene rs11362 A/G genetic variant is associated with risk of developing CAD: a case-control study. Acta Cardiol. 2024;79(6):730-6. doi:10.1080/00015385.2024.2375487

11. Pinkerton JW, Kim RY, Koeninger L, Armbruster NS, Hansbro NG, Brown AC, et al. Human beta-defensin-2 suppresses key features of asthma in murine models of allergic airways disease. Clin Exp Allergy. 2021;51(1):120-31. doi:10.1111/cea.13766

12. Borchers NS, Santos-Valente E, Toncheva AA, Wehkamp J, Franke A, Gaertner VD, et al. Human beta-Defensin 2 mutations are associated with asthma and atopy in children and its application prevents atopic asthma in a mouse model. Front Immunol. 2021;12:636061. doi:10.3389/fimmu.2021.636061

13. Kaczynska K, Zajac D, Wojciechowski P, Jampolska M. Regulatory peptides in asthma. Int J Mol Sci. 2021;22(24):13656. doi:10.3390/ijms222413656

14. Vilenskyi Y, Bordiy T, Shvaratska O, Bolbot Y. The content of antimicrobial peptides—human beta-defensin 2 and cathelicidin—in the secretion of the mucous membrane of the upper respiratory tract of children with bronchial asthma and allergic rhinitis. Pediatr Pol. 2021;96(1):23-30. doi:10.5114/polp.2021.104825

15. Holguin F, Cardet JC, Chung KF, Diver S, Ferreira DS, Fitzpatrick A, et al. Management of severe asthma: a European Respiratory Society/American Thoracic Society guideline. Eur Respir J. 2020;55(1):1900588. doi:10.1183/13993003.00588-2019

16. Wenzel SE. Severe adult asthmas: integrating clinical features, biology, and therapeutics to improve outcomes. Am J Respir Crit Care Med. 2021;203(7):809-21. doi:10.1164/rccm.202009-3631CI

17. Brusselle GG, Koppelman GH. Biologic therapies for severe asthma. N Engl J Med. 2022;386(2):157-71. doi:10.1056/NEJMra2032506

18. Menzies-Gow A, Corren J, Bourdin A, Chupp G, Israel E, Wechsler ME, et al. Tezepelumab in adults and adolescents with severe, uncontrolled asthma. N Engl J Med. 2021;384(19):1800-9. doi:10.1056/NEJMoa2034975

19. Diver S, Khalfaoui L, Emson C, Wenzel SE, Menzies-Gow A, Wechsler ME, et al. Effect of tezepelumab on airway inflammatory cells, remodelling, and hyperresponsiveness in patients with moderate-to-severe uncontrolled asthma (CASCADE): a double-blind, randomised, placebo-controlled, phase 2 trial. Lancet Respir Med. 2021;9(11):1299-312. doi:10.1016/S2213-2600(21)00226-5

20. Jackson DJ, Gern JE. Rhinovirus infections and their roles in asthma: etiology and exacerbations. J Allergy Clin Immunol Pract. 2022;10(3):673-81. doi:10.1016/j.jaip.2022.01.006

21. Menzies-Gow A, Wechsler ME, Brightling CE, Bourdin A, Maspero JF, Almqvist G, et al. Long-term safety and efficacy of tezepelumab in people with severe, uncontrolled asthma (DESTINATION): a randomised, placebo-controlled extension study. Lancet Respir Med. 2023;11(4):425-38. doi:10.1016/S2213-2600(22)00492-1

22. Wechsler ME, Menzies-Gow A, Brightling CE, Kuna P, Korn S, Welte T, et al. Evaluation of the oral corticosteroid-sparing effect of tezepelumab in adults with oral corticosteroid-dependent asthma (SOURCE): a randomised, placebo-controlled, phase 3 study. Lancet Respir Med. 2022;10(7):650-60. doi:10.1016/S2213-2600(21)00537-3

23. Fu J, Zong X, Jin M, Min J, Wang F, Wang Y. Mechanisms and regulation of defensins in host defense. Signal Transduct Target Ther. 2023;8(1):300. doi:10.1038/s41392-023-01553-x

24. Guo Q, Jin Y, Chen X, Ye X, Shen X, Lin M, et al. NF-kappaB in biology and targeted therapy: new insights and translational implications. Signal Transduct Target Ther. 2024;9:53. doi:10.1038/s41392-024-01757-9

25. Tan YY, Zhou HQ, Lin YJ, Yi LT, Chen ZG, Cao QD, et al. FGF2 is overexpressed in asthma and promotes airway inflammation through the FGFR/MAPK/NF-kappaB pathway in airway epithelial cells. Mil Med Res. 2022;9(1):7. doi:10.1186/s40779-022-00366-3

26. Dong X, Ding M, Zhang J, Ogulur I, Pat Y, Akdis M, Gao Y, Akdis CA. Involvement and therapeutic implications of airway epithelial barrier dysfunction in type 2 inflammation of asthma. Chin Med J (Engl). 2022;135(5):519-31. doi:10.1097/CM9.0000000000001983

27. Heijink IH, Kuchibhotla VNS, Roffel MP, Maes T, Knight DA, Sayers I, Nawijn MC. Epithelial cell dysfunction, a major driver of asthma development. Allergy. 2020;75(8):1902-17. doi:10.1111/all.14421

28. Liu L, Zhou L, Wang L, Mao Z, Zheng P, Zhang F, Liu H, Zhang H. MUC1 attenuates neutrophilic airway inflammation in asthma by reducing NLRP3 inflammasome-mediated pyroptosis through the inhibition of the TLR4/MyD88/NF-kappaB pathway. Respir Res. 2023;24:255. doi:10.1186/s12931-023-02550-y

29. Versi A, Ivan FX, Abdel-Aziz MI, Bates S, Riley J, Baribaud F, Zounemat Kermani N, Montuschi P, Dahlen SE, Djukanovic R, Sterk P, Maitland-Van Der Zee AH, Chotirmall SH, Howarth P, Adcock IM, Chung KF; U-BIOPRED consortium. Haemophilus influenzae and Moraxella catarrhalis in sputum of severe asthma with inflammasome and neutrophil activation. Allergy 2023;78(11):2906-20. doi:10.1111/all.15776

30. Jabeen MF, Tine M, Donachie G, Barber C, Azim A, Lau LCK, Brown T, Pavord ID, Chauhan A, Klenerman P, Street TL, Marchi E, Howarth PH, Hinks TSC. Species-level, metagenomic and proteomic analysis of microbe-immune interactions in severe asthma. Allergy. 2024;79(11):2966-80. doi:10.1111/all.16269

31. Kim YJ, Bunyavanich S. Microbial influencers: the airway microbiome's role in asthma. J Clin Invest. 2025;135(4):e184316. doi:10.1172/JCI184316

32. Tsuo K, Zhou W, Wang Y, Kanai M, Gupta R, Majara L, et al. Multi-ancestry meta-analysis of asthma identifies novel associations and highlights the value of increased power and diversity. Cell Genom. 2022;2(12):100212. doi:10.1016/j.xgen.2022.100212

33. Yan Q, Forno E, Herrera-Luis E, Pino-Yanes M, Qi C, Rios R, et al. A genome-wide association study of severe asthma exacerbations in Latino children and adolescents. Eur Respir J. 2021;57(4):2002693. doi:10.1183/13993003.02693-2020

34. Hernandez-Pacheco N, Li J, Repnik K, Vijverberg SJ, Berce V, Jorgensen A, et al. Genome-wide association study of asthma exacerbations despite inhaled corticosteroid use. Eur Respir J. 2021;57(5):2003388. doi:10.1183/13993003.03388-2020

35. Sordillo JE, Lutz SM, Jorgenson E, Iribarren C, McGeachie M, Dahlin A, et al. A polygenic risk score for asthma in a large racially diverse population. Clin Exp Allergy. 2021;51(11):1410-20. doi:10.1111/cea.14007

36. Namjou B, Lape M, Malolepsza E, DeVore SB, Weirauch MT, Dikilitas O, et al. Multiancestral polygenic risk score for pediatric asthma. J Allergy Clin Immunol. 2022;150(5):1086-96. doi:10.1016/j.jaci.2022.03.035

37. Olafsdottir TA, Theodors F, Bjarnadottir K, Bjornsdottir US, Agustsdottir AB, Stefansson OA, et al. Eighty-eight variants highlight the role of T cell regulation and airway remodeling in asthma pathogenesis. Nat Commun. 2020;11:393. doi:10.1038/s41467-019-14144-8

38. Tabyshova A, Emilov B, Postma MJ, Chavannes NH, Sooronbaev T, van Boven JFM. Prevalence and economic burden of respiratory diseases in Central Asia and Russia: a systematic review. Int J Environ Res Public Health. 2020;17(20):7483. doi:10.3390/ijerph17207483

39. Vinnikov D, Raushanova A, Mukatova I, Nurpeissov T, Kushekbayeva A, Toxarina A, Yessimova B, Bespayeva F, Brimkulov N. Asthma control in Kazakhstan: need for urgent action. BMC Pulm Med. 2023;23(1):7. doi:10.1186/s12890-022-02287-2

40. Dai SS, Sulaiman X, Isakova J, Xu WF, Najmudinov TA, Manilova EA, Khudoidodov BI, Chen X, Yang WK, Wang MS, Shen QK, Yang XY, Yao YG, Aldashev AA, Saidov A, Chen W, Cheng LF, Peng MS, Zhang YP. The genetic echo of the Tarim mummies in modern Central Asians. Mol Biol Evol. 2022;39(9):msac179. doi:10.1093/molbev/msac179

41. Kumar V, Bennett EA, Zhao D, Liang Y, Tang Y, Ren M, Dai Q, Feng X, Cao P, Yang R, Liu F, Ping W, Zhang M, Ding M, Yang MA, Amridin B, Muttalib H, Wang J, Fu Q. Genetic continuity of Bronze Age ancestry with increased steppe-related ancestry in Late Iron Age Uzbekistan. Mol Biol Evol. 2021;38(12):4908-17. doi:10.1093/molbev/msab216

42. Di YP, Kuhn JM, Mangoni ML. Lung antimicrobial proteins and peptides: from host defense to therapeutic strategies. Physiol Rev. 2024;104(4):1643-77. doi:10.1152/physrev.00039.2023

43. Zhang L, Jiang H, Yang G, Zhang J, Yuan S, Chen J, et al. Global, regional and national burden of asthma from 1990 to 2021: a systematic analysis for the Global Burden of Disease Study 2021. BMJ Open Respir Res. 2025;12(1):e003144. doi:10.1136/bmjresp-2025-003144

44. Feng S, Yang Y, Wang F, Shi W, Xu J, Tang G, Xie J, Xu J, Zhang N, Liang Z, Chen R. Low human beta-defensin-2 levels in the sputum of COPD patients are associated with the risk of exacerbations. BMC Pulm Med. 2023;23(1):106. doi:10.1186/s12890-023-02364-0

45. Ward A, Mauleon R, Ooi CY, Rosic N. Impact of gene modifiers on cystic fibrosis phenotypic profiles: a systematic review. Hum Mutat. 2024;2024:6165547. doi:10.1155/2024/6165547

46. Hong EP, Park JW. Sample size and statistical power calculation in genetic association studies. Genomics Inform. 2012;10(2):117-22. doi:10.5808/GI.2012.10.2.117

Nashr qilingan

2026-07-10