Ecological geneticsEcological geneticsЭкологическая генетика1811-09322411-9202Eco-Vector1169810.17816/ecogen17465-76Human ecological geneticsЭкологическая генетика человекаResearch ArticleGenetic susceptibility to juvenile idiopathic arthritis in the Belarusian population: gene-gene interactions analysisГенетическая предрасположенность к ювенильному идиопатическому артриту в белорусской популяции: анализ межгенных взаимодействий2331-6000YatskiuHanna A.ЯцкивАнна Андреевна
Belarus

Junior researcher, Laboratory of Molecular Basis of Genomic Stability

Младший научный сотрудник лаборатории молекулярных основ стабильности генома

a-yackiv@yandex.ru7004556893SavinaNataliya V.СавинаНаталья Викторовна
Belarus

Researcher, Laboratory of Molecular Basis of Genomic Stability

Научный сотрудник лаборатории молекулярных основ стабильности генома

n.savina@igc.by6602842335NikitchenkoNataliya V.НикитченкоНаталья Васильевна
Belarus

Researcher, Laboratory of Molecular Basis of Genomic Stability

Научный сотрудник лаборатории молекулярных основ стабильности генома

n.nikitchenko@igc.by6602670470KuzhirTatyana D.КужирТатьяна Дановна
Belarus

Doctor of Science, Main Researcher, Laboratory of Molecular Basis of Genomic Stability

доктор биологических наук, главный научный сотрудник лаборатории молекулярных основ стабильности генома

t.kuzhir@igc.byTchitchkoAlexei M.ЧичкоАлексей Михайлович
Belarus

PhD, Assistant Professor

Кандидат медицинских наук, доцент

childill1@bsmu.by57190016687SukaloAlexander V.СукалоАлександр Васильевич
Belarus

Academician, Doctor of Science, Professor, Head of the Department.

Академик, доктор медицинских наук, профессор, заведующий кафедры.

childill1@bsmu.by6701368733GoncharovaRoza I.ГончароваРоза Иосифовна
Belarus

Doctor of Science, Professor, Head of the Laboratory of Molecular Basis of Genomic Stability.

Доктор биологических наук, профессор, заведующий лабораторией молекулярных основ стабильности генома

r.goncharova@igc.byInstitute of Genetics and Cytology of the National Academy of Sciences of BelarusИнститут генетики и цитологии Национальной академии наук БеларусиInstitute of Genetics and Cytology ot the National Academy of Sciences of BelarusИнститут генетики и цитологии Национальной академии наук БеларусиBelarusian State Medical UniversityУО «Белорусский государственный медицинский университет»140920191512201917465761204201911092019Copyright ©; 2019, Yatskiu H.A., Savina N.V., Nikitchenko N.V., Kuzhir T.D., Tchitchko A.M., Sukalo A.V., Goncharova R.I.Copyright ©; 2019, Яцкив А.А., Савина Н.В., Никитченко Н.В., Кужир Т.Д., Чичко А.М., Сукало А.В., Гончарова Р.И.2019Yatskiu H.A., Savina N.V., Nikitchenko N.V., Kuzhir T.D., Tchitchko A.M., Sukalo A.V., Goncharova R.I.Яцкив А.А., Савина Н.В., Никитченко Н.В., Кужир Т.Д., Чичко А.М., Сукало А.В., Гончарова Р.И.http://creativecommons.org/licenses/by/4.0https://journals.eco-vector.com/ecolgenet/article/view/11698

Background. GWASs revealed a huge amount of candidate genes for juvenile idiopathic arthritis (JIA) susceptibility. Individual SNP analysis has restrictions as an effect of each substitution may be too subtle to be detected but their interactions may significantly contribute to disease susceptibility.

Materials and methods. 118 patients diagnosed with JIA and 202 controls were included into the study. The study was aimed to estimate interactions between SNPs of the immune and inflammatory responses genes: RUNX3 (rs11249215), RUNX1 (rs9979383), STAT4 (rs7574865), TRAF1/C5 (rs3761847), MIF (rs755622), CTLA4 (rs5742909, rs231775), PTPN2 (rs2542151) and to reveal their effects on the JIA susceptibility. SNPs were genotyped using PCR-RFLP and Real-time PCR. Multifactor dimensionality reduction analysis was performed using MDR 3.0.2 software.

Results. RUNX3, STAT4 and PTPN2 polymorphisms were associated with systemic arthritis, RF- polyarthritis and oligoarthritis respectively. Interaction of CTLA4 (rs5742909, rs231775), TRAF1/C5 (rs3761847), RUNX1 (rs9979383), PTPN2 (rs2542151) SNPs is shown to be a risk factor for JIA (p = 0.0099).

Conclusion. Some of the SNPs studied are associated with distinct JIA subtypes. MDR analysis identified a statistically significant high-order interaction of five polymorphisms which collectively may contribute to JIA genetic susceptibility in the Belarusian population.

Определены частоты распространения аллельных вариантов и их комбинаций в полиморфных локусах генов RUNX3, RUNX1, STAT4, TRAF1/C5, MIF, CTLA4, PTPN2 у 118 пациентов с ювенильным идиопатическим артритом (ЮИА). Выявлен неравнозначный вклад отдельных полиморфных вариантов в предрасположенность к различным подтипам ЮИА: с системным артритом ассоциированы минорный аллель A (p = 0,0057) и гомозиготы AA (p = 0,042) в локусе RUNX3 (rs11249215); в группе серонегативного полиартрита чаще встречается минорный аллель Т (p = 0,03) в локусе STAT4 (rs7574865); у детей с олигоартритом выше частота гомозигот по минорному аллелю G (p = 0,026) в локусе PTPN2 (rs2542151). Обнаружено 12 парных комбинаций генотипов, влияющих на вероятность развития ЮИА в общей выборке, при этом сочетания разных генотипов в пределах одной и той же пары локусов могут иметь противоположные эффекты. Несмотря на то что группа детей с ЮИА в целом и после стратификации по полу не отличалась от контрольных групп по результатам анализа отдельных локусов, изучение межгенных взаимодействий с помощью многофакторного сокращения размерности выявило сочетание генотипов по пяти локусам — CC (rs5742909) / AG (rs231775) / AG (rs3761847) / СТ (rs9979383) / TT (rs2542151), оцениваемое как рисковое (p = 0,0099). Полученные результаты подтверждают целесообразность учета комбинаций генотипов при оценке рисковой значимости однонуклеотидных замен.

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