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Альманах клинической медицины. 2019; 47: 548-558

Роль полиморфизма гена TNFα в положениях 238G/A и 308G/A в этиопатогенезе воспалительных заболеваний кишечника у различных этнических групп

Жилин И. В., Чашкова Е. Ю., Жилина А. А., Пушкарев Б. С., Коротаева Н. С.

https://doi.org/10.18786/2072-0505-2019-47-067

Аннотация

В обзоре литературы рассматриваются особенности течения воспалительных заболеваний кишечника (ВЗК) и полиморфизм гена фактора некроза опухоли альфа (TNFα) в  положениях 308G/A и 238G/A у пациентов различных этнических групп. По результатам поиска в  базах данных литературы PubMed, Medline, Еlibrary. ru отобрано 20 исследований, в  том числе 2  метаанализа, посвященных изучению роли полиморфизма гена TNFα308G/A и TNFα238G/A в этиопатогенезе ВЗК. Полиморфная вариация 308G/A соответствует повышенной секреции одноименного провоспалительного цитокина, генотип 238G/A характеризуется сниженной секрецией TNFα. Ряд исследователей указывают на наличие корреляции полиморфизма гена TNFα в положении 308G/A с тяжелым течением ВЗК, при котором необходимо более активное лечение пациентов (назначение цитостатиков, кортикостероидов, препаратов биологической терапии). В  некоторых публикациях отмечено, что у  пациентов-носителей варианта TNFα308G/A чаще возникает необходимость оперативных вмешательств. Взаимосвязь варианта TNFα308G/А с  фенотипическими особенностями ВЗК выявлена в  работах ряда исследовательских центров Европы, Азии, России. На азиатской популяции доказана корреляция данного полиморфизма с распространенностью язвенного колита. Подобные ассоциации отмечены в  единичных публикациях из Европы и  Северной Америки. Вместе с  тем существуют исследования, где связи TNFα308G/A и  TNFα238G/A с  течением ВЗК не обнаружено. TNFα238G/A не показал значимых результатов в  распространенности и  клиническом течении ВЗК. Предположительно, различия в  результатах, полученных в  исследованиях из одного географического региона, обусловлены генетической неоднородностью групп, фенотипической гетерогенностью испытуемых, а  также относительно небольшим размером выборки. В  настоящее время проводится поиск генетических, биохимических и других прогностических критериев течения ВЗК. Исследуются пути реализации генетической информации в особенностях проявления язвенного колита и  болезни Крона с  учетом расовой принадлежности.
Список литературы

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Almanac of Clinical Medicine. 2019; 47: 548-558

The role of TNF-alpha gene (-238G/A and -308G/A) polymorphisms in the etiology and pathogenesis of inflammatory bowel diseases in various ethnic groups

Zhilin I. V., Chashkova E. Yu., Zhilina A. A., Pushkarev B. S., Korotaeva N. S.

https://doi.org/10.18786/2072-0505-2019-47-067

Abstract

This literature review deals with specifics of the natural course of inflammatory bowel disease (IBD) in patients from various ethnic groups and -308G/A and -238G/A promoter polymorphisms in tumor necrosis factor-alpha (TNF-α) gene. The search in PubMed, Medline, Еlibrary.ru databases has led to identify in total 20 studies, including 2 meta-analyses, on the role of TNF-α-308G/A and -238G/A gene polymorphism in the etiology and pathophysiology of IBD. The TNF-α-308G/A polymorphism is associated with increased secretion of this proinflammatory cytokine, whereas the TNF-α-238G/A genotype is characterized by reduced TNF-α secretion. A  number of studies have shown an association between TNF-α-308G/A gene polymorphism and severe course of IBD, requiring more active treatment of patients (cytostatics, corticosteroids, biological agents). Some investigators have found that the patients carriers of TNF-α-308G/A had a  higher probability of surgical interventions. The association between TNF-α-308G/A and the phenotypic characteristics of IBD has been identified in studies performed in Europe, Asia, and Russia. The association of this polymorphism with the prevalence of ulcerative colitis has been proven in some studies, in particular, in the Asian population. Similar associations have been noted in few publications originating from Europe and North America, while some studies have found no links between TNF-α-308G/A, -238G/A, and the course of IBD. TNF-α-238G/A gene polymorphism has not shown any significance for the prevalence and course of ulcerative colitis and Crohn's disease. One can assume that the differences in the study results arising from one and the same geographical area are related to genetic heterogeneity of the study groups, phenotypic variances between the study subjects, as well as relatively small sample sizes. Currently, the search for genetic, biochemical and other prognostic criteria for IBD course is in progress. There are studies in progress to investigate the mechanisms of transformation of the genetic information into the particulars of ulcerative colitis and Crohn's disease manifestations, with consideration of ethnicity.
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