Complement activation lectin pathway (mannose-binding lectin and ficolin) genes polymorphism as the risk factor of CagA positive chronic Helicobacter pylori infection in adolescents

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Abstract

Currently, features of the host immune response against Helicobacter pylori (Hp) both regarding establishment of chronic carriage after primary infection as well as a role of impaired immune and inflammatory response in the mechanisms of developing erosive-ulcerative lesions remain poorly investigated. Only few molecules are known to activate the complement activation lectin pathway including human ficolins and mannose-binding lectin (MBL). A substantial part of the human population bears an intrinsically low MBL and ficolin production level and/or low functional activity due to the carriage of various MBL2 genetic variants potentially elevating susceptibility to a more severe course of a wide range of infectious diseases. It has been shown that the MBL2 gene polymorphisms are associated with a risk of developing in Hp-infected patients more severe gastric mucosal atrophy and gastric cancer risk. An impact of the MBL2 and L-ficolin (FNC2) gene variants on Hp infection rate in Russia has not yet been examined in full detail. In our study we enrolled 93 Caucasian adolescents (aged 12-17, Krasnoyarsk, Siberia, Russia) to test for serum anti-Hp-CagA antibodies. Additionally, 203 newborn dried blood spot specimens born in Krasnoyarsk, Russia, were used as a population control sample. Genotyping of allelic MBL2 and FCN2 gene variants was performed by using RFLP approach to examine the following polymorphic regions: rs11800451 and rs1800450 (MBL2), rs17549193 and rs7851696 (FCN2). Carriage of the rare allele in the polymorphic region rs1800450 of the MBL2 gene and the homozygous for the rare allele T of polymorphism rs17549193 in FCN2 gene was associated with an increased risk of CagA seropositivity (OR = 2.36 (1.03-5.4), p = 0.04 and OR = 5.69 (1.08-29.99), p = 0.04, respectively) shown before to be associated with low plasma concentrations and/or low functional activity of mannose-binding lectin and L-ficolin. In contrast, such genetic variants in the newborn population cohort had an intermediate prevalence further confirming the Caucasoid identity of the samples and an unbiased inclusion of subjects in the main test groups. Thus, we suggest that the primary MBL and L-ficolin deficiencies are associated with a higher risk of CagA positive Helicobacter pylori chronic infection in adolescents seemingly accounted for by alterations in lectin-mediated complement activation and opsonization especially in case of CagA positive bacterial strains.

About the authors

Sergey Yu. Tereshchenko

Scientific Research Institute of Medical Problems of the North, Federal Research Center Krasnoyarsk Science Center of the Siberian Branch of the Russian Academy of Sciences

Email: legise@mail.ru
ORCID iD: 0000-0002-1605-7859

SergeyYu. Tereshchenko - PhD, MD (Medicine), Head of Clinical Department of Childhood Somatic and Mental Health, Scientific Research Institute of Medical Problems of the North.

660022, Krasnoyarsk, Partizana Zheleznyaka str., 3g, Phone/fax: +7 (391) 228-06-83

Russian Federation

Marina V. Smolnikova

Scientific Research Institute of Medical Problems of the North, Federal Research Center Krasnoyarsk Science Center of the Siberian Branch of the Russian Academy of Sciences

Author for correspondence.
Email: smarinv@ya.ru
ORCID iD: 0000-0001-9984-2029

Smolnikova Marina V. - PhD (Biology), Leading Researcher, Laboratory of Molecular and Cell Pathology and Physiology, Scientific Research Institute of Medical Problems of the North.

Krasnoyarsk

Russian Federation

S. N. Zobova

Scientific Research Institute of Medical Problems of the North, Federal Research Center Krasnoyarsk Science Center of the Siberian Branch of the Russian Academy of Sciences; Krasnoyarsk State Medical University named after prof. V.F. Voino-Yasenetsky

Email: snzobova80@gmail.com
PhD (Medicine), Leading Researcher, Clinical Department of Somatic and Mental Health of Children, Scientific Research Institute of Medical Problems of the North, FRC «Krasnoyarsk Science Center» of the SB of the RAS; Researcher, Department of MGN, Institute of Postgraduate Education, Krasnoyarsk SMU named after prof. V.F. Voino-Yasenetsky Russian Federation

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Copyright (c) 2020 Tereshchenko S.Y., Smolnikova M.V., Zobova S.N.

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