Annals of the Russian academy of medical sciencesAnnals of the Russian academy of medical sciencesВестник Российской академии медицинских наук0869-60472414-3545"Paediatrician" Publishers LLC54810.15690/vramn548INFECTIOUS DISEASES: CURRENT ISSUESАКТУАЛЬНЫЕ ВОПРОСЫ ИНФЕКЦИОННЫХ БОЛЕЗНЕЙMathematic Model for Prediction of Liver Fibrosis Progression Rate in Patients with Chronic Hepatitis C Based on Combination of Genomic MarkersМатематическая модель прогноза скорости фиброза печени у больных с хроническим гепатитом С на основе комбинаций геномных маркеровSamokhodskaiaLarisa MikhaylovnaСамоходскаяЛариса Михайловна
Russian Federation

к.м.н., доц., Факультет фундаментальной медицины

slm@fbm.msu.ruStarostinaEkaterina Evgen'evnaСтаростинаЕкатерина Евгеньевна
Russian Federation

аспирант, Факультет фундаментальной медицины

starostinaee@gmail.comYarovayaElena BorisovnaЯроваяЕлена Борисовна
Russian Federation

д.ф.-м.н., доц., Механико-математический факультет

yarovaya@mech.math.msu.suKrasnovaTat'yana NikolaevnaКрасноваТатьяна Николаевна
Russian Federation

к.м.н., доц., Факультет фундаментальной медицины

krasnovamgu@yandex.ruMukhinNikolay AlekseevichМухинНиколай Алексеевич
Russian Federation

д.м.н., проф., академик РАН, Факультет фундаментальной медицины

moukhin-nephro@yandex.ruTkachukVsevolod Arsen'evichТкачукВсеволод Арсеньевич
Russian Federation

д.б.н., проф., академик РАН, декан ФФМ МГУ

vat@fbm.msu.ruSadovnichyViktor AntonovichСадовничийВиктор Антонович
Russian Federation

д.ф.-м.н., проф., академик РАН, ректор МГУ

info@rector.msu.ruLomonosov Moscow State UniversityМосковского  государственного университета  имени  М.В. ЛомоносоваLomonosov Moscow State UniversityМГУ имени М.В. ЛомоносоваSechenov First Moscow state medical universityГБОУ ВПО «Первый МГМУ имени И.М. Сеченова»311220157066516610312201503122015Copyright ©; 2015, "Paediatrician" Publishers LLCCopyright ©; 2015, Издательство "Педиатръ"2015"Paediatrician" Publishers LLCИздательство "Педиатръ"https://vestnikramn.spr-journal.ru/jour/about/submissionshttps://vestnikramn.spr-journal.ru/jour/article/view/548

Aim of study. To evaluate clinical significance of different combinations of gene polymorphisms IL-1b, IL-6, IL-10, TNF, HFE, TGF-b, ATR1, NOS3894, CYBA, AGT, MTHFR, FII, FV, FVII, FXIII, ITGA2, ITGB3, FBG, PAI and their prognostic value for prediction of liver fibrosis progression rate in patients with chronic hepatitis C (CHC).

Subjects and methods: 118 patients with CHC were divided into «fast» and «slow» (fibrosis rate progression ≥0,13 and <0,13 fibrosis units/yr; n =64 and n =54) fibrosis groups. Gene polymorphisms were determined. Statistical analysis was performed using Statistica 10.

Results. A allele (p =0,012) and genotype AA (p =0,024) of AGT G-6T gene, as well as T allele (p =0,013) and MT+TT genotypes (p =0,005) of AGT 235 M/T gene were significantly more common in «fast fibrosers» than in «slow fibrosers». Patients with genotype TT of CYBA 242 C/T had a higher fibrosis progression rate than patients with CC+CT genotype (p =0,02). Our analysis showed a protective effect of TT genotype of ITGA2 807 C/T on fibrosis progression rate (p =0,03). There was a trend (p <0,15) to higher fibrosis progression rate in patients with mutant alleles and genotypes of TGFb +915 G/C, FXIII 103 G/T, PAI -675 5G/4G genes. Other gene polymorphisms were not associated with enhanced liver fibrosis. To build a mathematical model for prediction of liver fibrosis progression rate we performed coding with scores for genotypes and virus genotype. Total score correlated with the fibrosis progression rate (R =0,39, p =0,000).

Conclusion: Determination of genetic profile of the patient and virus genotype allows to predict the course of CHC.

Обоснование. В настоящее время большое внимание уделяется поиску генетических факторов, объясняющих течение хронического гепатита С (ХГС).

Цель исследования: оценить прогностическую значимость носительства комбинаций аллельных вариантов генов IL 1b, IL 6, IL 10, TNF α, HFE, TGF b, ATR1, NOS3, CYBA, AGT, MTHFR, FII, FV, FVII, FXIII, ITGA2, ITGB3, FBG, PAI на прогрессирование фиброза печени при ХГС.

Материалы и методы: 118 пациентов с ХГС разделены на группы с быстрым и медленным (скорость фиброза ≥0,13 и <0,13 ед. фиброза/год; n =64 и n =54, соответственно) фиброзом. Выполнено определение полиморфизма. Статистическую обработку результатов проводили с использованием пакетов программ Statistica 10.

Результаты. У больных с быстрым фиброзом в сравнении с группой с медленным чаще встречались аллель А (р =0,012) и мутантный генотип АА (р =0,024) гена AGT G-6T, также в данной группе чаще выявляли аллель Т (р =0,013) и генотип МТ+ТТ гена AGT 235 M/T (р =0,005). Больные с генотипом ТТ гена CYBA 242 C/T имели более высокую скорость фиброза по сравнению с больными с генотипом СС+СТ (р =0,02). В ходе анализа выявлено протективное влияние гомозиготы ТТ гена ITGA2 807 C/T на темпы фиброза (р =0,03). Наблюдались тенденции к различию по встречаемости аллелей и генотипов полиморфных маркеров TGFb +915 G/С, FXIII 103 G/T, PAI -675 5G/4G между двумя группами. Для остальных генов достоверных отличий не обнаружено. В дальнейшем построена математическая модель, учитывающая протективное и профиброгенное влияние генов, в также влияние генотипа вируса. Выявлена корреляция между суммой баллов в этой модели и темпом прогрессирования фиброза в печени (R =0,39, p =0,000).

Заключение: предложенная математическая модель может прогнозировать течение болезни.

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