docruДоктор.РуTitle1727-23782713-2994ООО "ГК "РУСМЕДИКАЛ"10.31550/1727-2378-2024-23-3-24-31docru-111Research ArticleОРИГИНАЛЬНЫЕ СТАТЬИORIGINAL PAPERSРоль генетически детерминированного дефицита лектинового пути активации комплемента при хронической инфекции Helicobacter pylori у детейThe Role of Genetically Determined Deficiency of the Lectin Pathway of Complement Activation in Chronic Helicobacter pylori Among Childrenhttps://orcid.org/0000-0002-1605-7859ТерещенкоС. Ю.TereshchenkoS. Yu.

Терещенко Сергей Юрьевич — д. м. н., профессор, заведующий клиническим отделением соматического и психического здоровья детей

660022, г. Красноярск, ул. Партизана Железняка, д. 3г

3g Partisan Zheleznyak Str., Krasnoyarsk, 660022

legise@mail.ruhttps://orcid.org/0000-0001-9984-2029СмольниковаМ. В.SmolnikovaM. V.

Смольникова Марина Викторовна — к. б. н., ведущий научный сотрудник, руководитель группы молекулярно-генетических исследований

660022, г. Красноярск, ул. Партизана Железняка, д. 3г

3g Partisan Zheleznyak Str., Krasnoyarsk, 660022

smarinv@yandex.ruhttps://orcid.org/0000-0003-3920-0694ГорбачеваН. Н.GorbachevaN. N.

Горбачева Нина Николаевна — старший научный сотрудник клинического отделения соматического и психического здоровья детей

660022, г. Красноярск, ул. Партизана Железняка, д. 3г

3g Partisan Zheleznyak Str., Krasnoyarsk, 660022

n-n-gorbacheva@yandex.ruНаучно-исследовательский институт медицинских проблем Севера — обособленное подразделение ФГБНУ «Федеральный исследовательский центр «Красноярский научный центр Сибирского отделения Российской академии наук»РоссияScientific and Research Institute of Medical Problems of the North, Federal Research Centre “Krasnoyarsk Scientific Centre of the Siberian Branch of the Russian Academy of Science”Russian Federation202416022025233ПЕДИАТРИЯ2431Copyright © Терещенко С.Ю., Смольникова М.В., Горбачева Н.Н., 20252025Терещенко С.Ю., Смольникова М.В., Горбачева Н.Н.Tereshchenko S.Y., Smolnikova M.V., Gorbacheva N.N.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://docru.elpub.ru/jour/article/view/111Цель исследования

Цель исследования: изучить связи 6 полиморфных регионов гена маннозосвязывающего лектина (MBL2) (rs11003125, rs7096206, rs7095891, rs1800450, rs1800451, rs5030737), 2 регионов гена L-фиколина (FCN2) (rs7851696, rs17549193) и 1 региона гена маннозосвязывающей лектин-ассоциированной сериновой протеазы (MASP2) (rs72550870) c Helicobacter pylori-инфицированностью и выраженностью нейтрофильного воспаления в слизистой желудка у детей с рецидивирующими болями в животе.

Дизайн

Дизайн. Генетическое ассоциативное исследование однонуклеотидных полиморфизмов типа «случай — контроль».

Материалы и методы

Материалы и методы. Обследовано 96 подростков в возрасте 12–17 лет с рецидивирующей абдоминальной болью. Обследование включало сбор анамнеза, общеклинические методы и фиброгастроскопию с биопсией слизистой оболочки желудка. Биоптаты фиксировали и обрабатывали для оценки нейтрофильной инфильтрации и наличия H. pylori. Результаты интерпретировали согласно Сиднейской системе классификации хронического гастрита. Генотипирование аллельных вариантов генов осуществлено методом полимеразной цепной реакции в режиме реального времени (MBL2, MASP2), а также с помощью рестрикционного анализа продуктов амплификации специфических участков генома (MBL2, FCN2).

Результаты

Результаты. Высокая степень колонизации H. pylori ассоциировалась с высокой частотой аллеля L полиморфного региона rs11003125 гена MBL2 и со снижением доли MBL-высокоэкспрессирующих генотипов. Носительство аллеля Q участка rs7095891 гена MBL2 ассоциировалось с менее выраженной нейтрофильной инфильтрацией, а высокая частота аллеля T полиморфного участка rs7851696 гена FCN2 — с выраженным нейтрофильным воспалением слизистой оболочки желудка. В распределении генотипов MASP2 различий не установлено.

Заключение

Заключение. Полученные результаты позволяют предположить, что генетические дефекты продукции MBL и фиколина-2 могут способствовать формированию хронического хеликобактериоза у детей и более выраженному воспалению слизистой оболочки желудка. Дальнейшее изучение роли этих белков представляется перспективным для определения новых подходов к терапии и профилактике осложнений инфекции H. pylori у детей.

Aim

Aim. To study the association of six polymorphic regions of MBL2 (rs11003125, rs7096206, rs7095891, rs1800450, rs1800451, rs5030737), two regions of FCN2 (rs7851696, rs17549193) and one region of MASP2 (rs72550870) with Helicobacter pylori infection and the severity of neutrophilic inflammation in gastric mucosa among children with recurrent abdominal pain.

Design

Design. Genetic association study of single nucleotide polymorphisms, case — control type.

Materials and methods

Materials and methods. 96 adolescents aged 12–17 years with recurrent abdominal pain were examined. Medical history, general clinical methods and fibrogastroscopy with a biopsy of the gastric mucosa were included in the medical testing. Biopsy samples were recorded and processed to assess the neutrophil infiltration and the presence of H. pylori. The results were interpreted according to the Sydney System of Gastritis Classification. Genotyping of allelic gene variants was carried out using real-time polymerase chain reaction (MBL2, MASP2), as well as the restriction analysis of amplification products of specific genome regions (MBL2, FCN2).

Results

Results. A high rate of H. pylori colonization was associated with a high frequency of the L allele of the rs11003125 gene polymorphism of the MBL2 gene and with a decrease in the proportion of high MBL — expressing genotypes. Carriage of the Q allele of the rs7095891 gene polymorphism of the MBL2 gene was associated with less pronounced neutrophilic infiltration, and a high frequency of the T allele of the rs7851696 gene polymorphism of the FCN2 gene was associated with severe neutrophilic inflammation in gastric mucosa. No differences in the distribution of MASP2 genotypes were found.

Conclusion

Conclusion. The results obtained suggest that genetic defects in the production of MBL and ficolin-2 may cause chronic helicobacteriosis in children and more severe inflammation of gastric mucosa. Further study of these proteins seems to be promising for new approaches to the treatment and prevention of H. pylori complications in children to be identified.

Helicobacter pyloriманнозосвязывающий лектинфиколинMASPполиморфизм геновHelicobacter pylorimannose-binding lectinficolinMASPgene polymorphismReferencesZabala Torrres B., Lucero Y., Lagomarcino A.J. et al. Review: prevalence and dynamics of Helicobacter pylori infection during childhood. Helicobacter. 2017;22(5). DOI: 10.1111/hel.12399Zabala Torrres B., Lucero Y., Lagomarcino A.J. et al. Review: prevalence and dynamics of Helicobacter pylori infection during childhood. Helicobacter. 2017;22(5). DOI: 10.1111/hel.12399Aguilera Matos I., Diaz Oliva S.E., Escobedo A.A. et al. Helicobacter pylori infection in children. BMJ Paediatrics Open. 2020;4(1):e000679. DOI: 10.1136/bmjpo-2020-000679Aguilera Matos I., Diaz Oliva S.E., Escobedo A.A. et al. Helicobacter pylori infection in children. BMJ Paediatrics Open. 2020;4(1):e000679. DOI: 10.1136/bmjpo-2020-000679Nguyen J., Kotilea K., Bontems P., Miendje Deyi V.Y. Helicobacter pylori Infections in Children. Antibiotics (Basel). 2023;12(9):1440. DOI: 10.3390/antibiotics12091440Nguyen J., Kotilea K., Bontems P., Miendje Deyi V.Y. Helicobacter pylori Infections in Children. Antibiotics (Basel). 2023;12(9):1440. DOI: 10.3390/antibiotics12091440Garred P., Genster N., Pilely K. et al. A journey through the lectin pathway of complement-MBL and beyond. Immunol. Rev. 2016;274(1):74–97. DOI: 10.1111/imr.12468Garred P., Genster N., Pilely K. et al. A journey through the lectin pathway of complement-MBL and beyond. Immunol. Rev. 2016;274(1):74–97. DOI: 10.1111/imr.12468Терещенко С.Ю., Смольникова М.В. Врожденные дисфункции паттерн-распознающих рецепторов в патогенезе инвазивной и рецидивирующей пневмококковой инфекции у детей. Инфекция и иммунитет. 2019;9(2):229–238.Tereshchenko S.Yu., Smolnikova M.V. Congenitally impaired pattern-recognition receptors in pathogenesis of pediatric invasive and recurrent pneumococcal infection. Russian Journal of Infection and Immunity. 2019;9(2):229–238. (in Russian). DOI: 10.15789/2220-7619-2019-2-229-238Смольникова М.В., Терещенко С.Ю. Протеины лектинового пути активации системы комплемента: иммунобиологические функции, генетика и участие в патогенезе заболеваний человека. Инфекция и иммунитет. 2022;12(2):209–221.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):209–221. (in Russian). DOI: 10.15789/2220-7619-POT-1777Kilpatrick D.C. Mannan-binding lectin: clinical significance and applications. Biochim. Biophys. Acta. 2002;1572(2–3):401–413. DOI: 10.1016/s0304-4165(02)00321-5Kilpatrick D.C. Mannan-binding lectin: clinical significance and applications. Biochim. Biophys. Acta. 2002;1572(2–3):401–413. DOI: 10.1016/s0304-4165(02)00321-5Stengaard-Pedersen K., Thiel S., Gadjeva M. et al. nherited deficiency of mannan-binding lectin-associated serine protease 2. N. Engl. J. Med. 2003;349(6):554–560. DOI: 10.1056/NEJMoa022836Stengaard-Pedersen K., Thiel S., Gadjeva M. et al. nherited deficiency of mannan-binding lectin-associated serine protease 2. N. Engl. J. Med. 2003;349(6):554–560. DOI: 10.1056/NEJMoa022836Thiel S., Kolev M., Degn S. et al. Polymorphisms in mannan-binding lectin (MBL)-associated serine protease 2 affect stability, binding to MBL, and enzymatic activity. J. Immunol. 2009;182(5):2939–2947. DOI: 10.4049/jimmunol.0802053Thiel S., Kolev M., Degn S. et al. Polymorphisms in mannan-binding lectin (MBL)-associated serine protease 2 affect stability, binding to MBL, and enzymatic activity. J. Immunol. 2009;182(5):2939–2947. DOI: 10.4049/jimmunol.0802053Cedzyński M., Świerzko A.S. Components of the lectin pathway of complement in solid tumour cancers. Cancers (Basel). 2022;14(6):1543. DOI: 10.3390/cancers14061543Cedzyński M., Świerzko A.S. Components of the lectin pathway of complement in solid tumour cancers. Cancers (Basel). 2022;14(6):1543. DOI: 10.3390/cancers14061543Bak-Romaniszyn L., Swierzko A., Szemraj J. et al. Mannan-binding lectin (MBL) in duodenal ulcer and gastritis. Polski Merkuriusz Lekarski Polish Medical Journal. 2009;26(155):412–415.Bak-Romaniszyn L., Swierzko A., Szemraj J. et al. Mannan-binding lectin (MBL) in duodenal ulcer and gastritis. Polski Merkuriusz Lekarski Polish Medical Journal. 2009;26(155):412–415.Scudiero O., Nardone G., Omodei D. et al. A mannose-binding lectin-defective haplotype is a risk factor for gastric cancer. Clin. Chem. 2006;52(8):1625–1627. DOI: 10.1373/clinchem.2006.071696Scudiero O., Nardone G., Omodei D. et al. A mannose-binding lectin-defective haplotype is a risk factor for gastric cancer. Clin. Chem. 2006;52(8):1625–1627. DOI: 10.1373/clinchem.2006.071696Wang F.Y., Tahara T., Arisawa T. et al. Mannan-binding lectin (MBL) polymorphism and gastric cancer risk in Japanese population. Dig. Dis. Sci. 2008;53(11):2904–2908. DOI: 10.1007/s10620-008-0249-3Wang F.Y., Tahara T., Arisawa T. et al. Mannan-binding lectin (MBL) polymorphism and gastric cancer risk in Japanese population. Dig. Dis. Sci. 2008;53(11):2904–2908. DOI: 10.1007/s10620-008-0249-3Tahara T., Shibata T., Wang F.Y. et al. Mannan-binding lectin B allele is associated with a risk of developing more severe gastric mucosal atrophy in Helicobacter pylori-infected Japanese patients. Eur. J. Gastroenterol. Hepatol. 2009;21(7):781–786. DOI: 10.1097/MEG.0b013e328309c76bTahara T., Shibata T., Wang F.Y. et al. Mannan-binding lectin B allele is associated with a risk of developing more severe gastric mucosal atrophy in Helicobacter pylori-infected Japanese patients. Eur. J. Gastroenterol. Hepatol. 2009;21(7):781–786. DOI: 10.1097/MEG.0b013e328309c76bKuipers S., Aerts P.C., van Dijk H. Differential microorganism-induced mannose-binding lectin activation. FEMS Immunol. Med. Microbiol. 2003;36(1):33–39. DOI: 10.1016/S0928-8244(03)00032-4Kuipers S., Aerts P.C., van Dijk H. Differential microorganism-induced mannose-binding lectin activation. FEMS Immunol. Med. Microbiol. 2003;36(1):33–39. DOI: 10.1016/S0928-8244(03)00032-4Dixon M.F., Genta R.M., Yardley J.H., Correa P. Classification and grading of gastritis. The updated Sydney System. International Workshop on the Histopathology of Gastritis, Houston 1994. Am. J. Surg. Pathol. 1996;20(10):1161–1181. DOI: 10.1097/00000478-199610000-00001Dixon M.F., Genta R.M., Yardley J.H., Correa P. Classification and grading of gastritis. The updated Sydney System. International Workshop on the Histopathology of Gastritis, Houston 1994. Am. J. Surg. Pathol. 1996;20(10):1161–1181. DOI: 10.1097/00000478-199610000-00001Wallis R., Lynch N.J. Biochemistry and genetics of the collectins. In: Kilpatrick D. (ed.) Collagen-related lectins in innate immunity. Research Signpost; 2007:33–56.Wallis R., Lynch N.J. Biochemistry and genetics of the collectins. In: Kilpatrick D. (ed.) Collagen-related lectins in innate immunity. Research Signpost; 2007:33–56.Garred P., Honoré C., Ma Y.J. et al. MBL2, FCN1, FCN2 and FCN3 — the genes behind the initiation of the lectin pathway of complement. Mol. Immunol. 2009;46(14):2737–2744. DOI: 10.1016/j.molimm.2009.05.005Garred P., Honoré C., Ma Y.J. et al. MBL2, FCN1, FCN2 and FCN3 — the genes behind the initiation of the lectin pathway of complement. Mol. Immunol. 2009;46(14):2737–2744. DOI: 10.1016/j.molimm.2009.05.005Monsey L., Best L.G., Zhu J. et al. The association of mannose binding lectin genotype and immune response to Chlamydia pneumoniae: The Strong Heart Study. PLoS One. 2019;14(1):e0210640. DOI: 10.1371/journal.pone.0210640Monsey L., Best L.G., Zhu J. et al. The association of mannose binding lectin genotype and immune response to Chlamydia pneumoniae: The Strong Heart Study. PLoS One. 2019;14(1):e0210640. DOI: 10.1371/journal.pone.0210640Eisen D.P., Minchinton R.M. Impact of mannose-binding lectin on susceptibility to infectious diseases. Clin. Infect. Dis. 2003;37(11):1496–1505. DOI: 10.1086/379324Eisen D.P., Minchinton R.M. Impact of mannose-binding lectin on susceptibility to infectious diseases. Clin. Infect. Dis. 2003;37(11):1496–1505. DOI: 10.1086/379324Eisen D.P. Mannose-binding lectin deficiency and respiratory tract infection. J. Innate Immun. 2010;2(2):114–122. DOI: 10.1159/000228159Eisen D.P. Mannose-binding lectin deficiency and respiratory tract infection. J. Innate Immun. 2010;2(2):114–122. DOI: 10.1159/000228159Kalia N., Singh J., Kaur M. The ambiguous role of mannose-binding lectin (MBL) in human immunity. Open Med. 2021;16(1):299–310. DOI: 10.1515/med-2021-0239Kalia N., Singh J., Kaur M. The ambiguous role of mannose-binding lectin (MBL) in human immunity. Open Med. 2021;16(1):299–310. DOI: 10.1515/med-2021-0239Brodszki N., Frazer-Abel A., Grumach A.S. et al. European Society for Immunodeficiencies (ESID) and European Reference Network on Rare Primary Immunodeficiency, Autoinflammatory and Autoimmune Diseases (ERN RITA) Complement Guideline: Deficiencies, Diagnosis, and Management. J. Clin. Immunol. 2020;40(4):576–591. DOI: 10.1007/s10875-020-00754-1Brodszki N., Frazer-Abel A., Grumach A.S. et al. European Society for Immunodeficiencies (ESID) and European Reference Network on Rare Primary Immunodeficiency, Autoinflammatory and Autoimmune Diseases (ERN RITA) Complement Guideline: Deficiencies, Diagnosis, and Management. J. Clin. Immunol. 2020;40(4):576–591. DOI: 10.1007/s10875-020-00754-1Rantala A., Lajunen T., Juvonen R. et al. Mannose-binding lectin concentrations, MBL2 polymorphisms, and susceptibility to respiratory tract infections in young men. J. Infect. Dis. 2008;198(8):1247–1253. DOI: 10.1086/591912Rantala A., Lajunen T., Juvonen R. et al. Mannose-binding lectin concentrations, MBL2 polymorphisms, and susceptibility to respiratory tract infections in young men. J. Infect. Dis. 2008;198(8):1247–1253. DOI: 10.1086/591912Zhang N., Zhuang M., Ma A. et al. Association of levels of mannose-binding lectin and the MBL2 gene with type 2 diabetes and diabetic nephropathy. PLoS One. 2013;8(12):e83059. DOI: 10.1371/journal.pone.0083059Zhang N., Zhuang M., Ma A. et al. Association of levels of mannose-binding lectin and the MBL2 gene with type 2 diabetes and diabetic nephropathy. PLoS One. 2013;8(12):e83059. DOI: 10.1371/journal.pone.0083059Olszowski T., Adler G., Janiszewska-Olszowska J. et al. MBL2, MASP2, AMELX, and ENAM gene polymorphisms and dental caries in Polish children. Oral Dis. 2012;18(4):389–395. DOI: 10.1111/j.1601-0825.2011.01887.xOlszowski T., Adler G., Janiszewska-Olszowska J. et al. MBL2, MASP2, AMELX, and ENAM gene polymorphisms and dental caries in Polish children. Oral Dis. 2012;18(4):389–395. DOI: 10.1111/j.1601-0825.2011.01887.xYang Y., Wang W., Qin M. Mannose-binding lectin gene polymorphisms are not associated with susceptibility to severe early childhood caries. Hum. Immunol. 2013;74(1):110–13. DOI: 10.1016/j.humimm.2012.08.012Yang Y., Wang W., Qin M. Mannose-binding lectin gene polymorphisms are not associated with susceptibility to severe early childhood caries. Hum. Immunol. 2013;74(1):110–13. DOI: 10.1016/j.humimm.2012.08.012Alyousef Y.M., Borgio J.F., AbdulAzeez S. et al. Association of MBL2 Gene Polymorphism with Dental Caries in Saudi Children. Car. Res. 2017;51(1):12–16. DOI: 10.1159/000450963Alyousef Y.M., Borgio J.F., AbdulAzeez S. et al. Association of MBL2 Gene Polymorphism with Dental Caries in Saudi Children. Car. Res. 2017;51(1):12–16. DOI: 10.1159/000450963Mokhtari M.J., Koohpeima F., Hashemi-Gorji F. Association of the risk of dental caries and polymorphism of MBL2 rs11003125 gene in iranian adults. Car. Res. 2019;53(1):60–64. DOI: 10.1159/000489572Mokhtari M.J., Koohpeima F., Hashemi-Gorji F. Association of the risk of dental caries and polymorphism of MBL2 rs11003125 gene in iranian adults. Car. Res. 2019;53(1):60–64. DOI: 10.1159/000489572Yokoyama E., Chávez-Saldaña M., Orozco L. et al. Influence of SNPs in genes that modulate lung disease severity in a group of Mexican patients with cystic fibrosis. Arch. Med. Res. 2018;49(1):18–26. DOI: 10.1016/j.arcmed.2018.04.010Yokoyama E., Chávez-Saldaña M., Orozco L. et al. Influence of SNPs in genes that modulate lung disease severity in a group of Mexican patients with cystic fibrosis. Arch. Med. Res. 2018;49(1):18–26. DOI: 10.1016/j.arcmed.2018.04.010El-Behedy E.M., Akeel N., El-Maghraby H.M., Shawky A. Serum level and genetic polymorphism of mannose-binding lectin in infants with neonatal sepsis at Zagazig University Hospitals. Egypt. J. Immunol. 2019;26(1):91–99.El-Behedy E.M., Akeel N., El-Maghraby H.M., Shawky A. Serum level and genetic polymorphism of mannose-binding lectin in infants with neonatal sepsis at Zagazig University Hospitals. Egypt. J. Immunol. 2019;26(1):91–99.Speletas M., Dadouli K., Syrakouli A. et al. MBL deficiency-causing B allele (rs1800450) as a risk factor for severe COVID-19. Immunobiology. 2021;226(6):152136. DOI: 10.1016/j.imbio.2021.152136Speletas M., Dadouli K., Syrakouli A. et al. MBL deficiency-causing B allele (rs1800450) as a risk factor for severe COVID-19. Immunobiology. 2021;226(6):152136. DOI: 10.1016/j.imbio.2021.152136Cedzynski M., Nuytinck L., Atkinson A.P. et al. Extremes of l-ficolin concentration in children with recurrent infections are associated with single nucleotide polymorphisms in the FCN2 gene. Clin. Exp. Immunol. 2007;150(1):99–104. DOI: 10.1111/j.1365-2249.2007.03471.xCedzynski M., Nuytinck L., Atkinson A.P. et al. Extremes of l-ficolin concentration in children with recurrent infections are associated with single nucleotide polymorphisms in the FCN2 gene. Clin. Exp. Immunol. 2007;150(1):99–104. DOI: 10.1111/j.1365-2249.2007.03471.xKilpatrick D.C., St Swierzko A., Matsushita M. et al. The relationship between FCN2 genotypes and serum ficolin-2 (L-ficolin) protein concentrations from a large cohort of neonates. Human Immunol. 2013;74(7):867–871. DOI: 10.1016/j.humimm.2013.04.011Kilpatrick D.C., St Swierzko A., Matsushita M. et al. The relationship between FCN2 genotypes and serum ficolin-2 (L-ficolin) protein concentrations from a large cohort of neonates. Human Immunol. 2013;74(7):867–871. DOI: 10.1016/j.humimm.2013.04.011Świerzko A.S., Jarych D., Gajek G. 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.2021.741140Świerzko A.S., Jarych D., Gajek G. 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.2021.741140Haerynck F., Van Steen K., Cattaert T. et al. Polymorphisms in the lectin pathway genes as a possible cause of early chronic Pseudomonas aeruginosa colonization in cystic fibrosis patients. Hum. Immun. 2012;73(11):1175–1183. DOI: 10.1016/j.humimm.2012.08.010Haerynck F., Van Steen K., Cattaert T. et al. Polymorphisms in the lectin pathway genes as a possible cause of early chronic Pseudomonas aeruginosa colonization in cystic fibrosis patients. Hum. Immun. 2012;73(11):1175–1183. DOI: 10.1016/j.humimm.2012.08.010Baccarelli A., Hou L., Chen J. et al. Mannose-binding lectin-2 genetic variation and stomach cancer risk. Int. J. Cancer. 2006;119(8):1970–1975. DOI: 10.1002/ijc.22075Baccarelli A., Hou L., Chen J. et al. Mannose-binding lectin-2 genetic variation and stomach cancer risk. Int. J. Cancer. 2006;119(8):1970–1975. DOI: 10.1002/ijc.22075Mortazavi E., Eslami B., Aghahosseini P. et al. Association of mannose-binding lectin rs1800450 and tumor necrotic factor-α rs1800620 polymorphism with Helicobacter pylori in type II diabetes mellitus. Monoclon. Antib. Immunodiagn. Immunother. 2017;36(5):236–241. DOI: 10.1089/mab.2017.0039Mortazavi E., Eslami B., Aghahosseini P. et al. Association of mannose-binding lectin rs1800450 and tumor necrotic factor-α rs1800620 polymorphism with Helicobacter pylori in type II diabetes mellitus. Monoclon. Antib. Immunodiagn. Immunother. 2017;36(5):236–241. DOI: 10.1089/mab.2017.0039Worthley D.L., Bardy P.G., Gordon D.L., Mullighan C.G. Mannose-binding lectin and gastric cancer. Int. J. Cancer. 2007;120(12): 2751–2752. DOI: 10.1002/ijc.22662Worthley D.L., Bardy P.G., Gordon D.L., Mullighan C.G. Mannose-binding lectin and gastric cancer. Int. J. Cancer. 2007;120(12): 2751–2752. DOI: 10.1002/ijc.22662Chang Y.W., Oh C.H., Kim J-W. et al. Combination of Helicobacter pylori infection and the interleukin 8–251T>A polymorphism, but not the mannose-binding lectin 2 codon 54G>A polymorphism, might be a risk factor of gastric cancer. BMC Cancer. 2017;17(1):388. DOI: 10.1186/s12885-017-3378-2Chang Y.W., Oh C.H., Kim J-W. et al. Combination of Helicobacter pylori infection and the interleukin 8–251T>A polymorphism, but not the mannose-binding lectin 2 codon 54G>A polymorphism, might be a risk factor of gastric cancer. BMC Cancer. 2017;17(1):388. DOI: 10.1186/s12885-017-3378-2Tahara T., Shibata T., Wang F. et al. Genetic polymorphisms of molecules associated with innate immune responses, TRL2 and MBL2 genes in Japanese subjects with functional dyspepsia. J. Clin. Biochem. Nutr. 2010;47(3):217–223. DOI: 10.3164/jcbn.10-40Tahara T., Shibata T., Wang F. et al. Genetic polymorphisms of molecules associated with innate immune responses, TRL2 and MBL2 genes in Japanese subjects with functional dyspepsia. J. Clin. Biochem. Nutr. 2010;47(3):217–223. DOI: 10.3164/jcbn.10-40Ko G.H., Kang S.M., Kim Y.K. et al. Invasiveness of Helicobacter pylori into human gastric mucosa. Helicobacter. 1999;4(2):77–81. DOI: 10.1046/j.1523-5378.1999.98690.xKo G.H., Kang S.M., Kim Y.K. et al. Invasiveness of Helicobacter pylori into human gastric mucosa. Helicobacter. 1999;4(2):77–81. DOI: 10.1046/j.1523-5378.1999.98690.xBak-Romaniszyn L., Cedzyński M., Szemraj J. et al. Mannan-binding lectin in children with chronic gastritis. Scand. J. Immunol. 2006;63(2):131–135. DOI: 10.1111/j.1365-3083.2005.01719.xBak-Romaniszyn L., Cedzyński M., Szemraj J. et al. Mannan-binding lectin in children with chronic gastritis. Scand. J. Immunol. 2006;63(2):131–135. DOI: 10.1111/j.1365-3083.2005.01719.x

The authors declare that there are no conflicts of interest present.