vavilovВавиловский журнал генетики и селекцииVavilov Journal of Genetics and Breeding2500-3259Institute of Cytology and Genetics of Siberian Branch of the RAS10.18699/vjgb-26-83vavilov-5236Research ArticleМЕДИЦИНСКАЯ ГЕНЕТИКАMEDICAL GENETICSАллель APOE ε2 ассоциирован в российской когорте с риском неоваскулярной возрастной макулярной дегенерацииThe APOE ε2 allele is associated with risk of neovascular age-related macular degeneration in a Russian cohortКожевниковаО. С.KozhevnikovaO. S.

Новосибирск

Novosibirsk

НикуличИ. В.NikulichI. F.

Новосибирск

Novosibirsk

ДербенёваА. С.DerbenevaA. S.

Новосибирск

Novosibirsk

ДевяткинВ. А.DevyatkinV. A.

Новосибирск

Novosibirsk

КолоcоваН. Г.KolosovaN. .G.

Новосибирск

Novosibirsk

ФурсоваА. Ж.FursovaА. Zh.

Новосибирск

Novosibirsk

anzhellafursova@yandex.ruФедеральный исследовательский центр Институт цитологии и генетики Сибирского отделения Российской академии наукРоссияInstitute of Cytology and Genetics of the Siberian Branch of the Russian Academy of SciencesRussian FederationГосударственная Новосибирская областная клиническая больница, Новосибирск; Новосибирский государственный медицинский университетРоссияState Novosibirsk Regional Clinical Hospital; Novosibirsk State Medical UniversityRussian FederationФедеральный исследовательский центр Институт цитологии и генетики Сибирского отделения Российской академии наук; Государственная Новосибирская областная клиническая больница, Новосибирск; Новосибирский государственный медицинский университетРоссияInstitute of Cytology and Genetics of the Siberian Branch of the Russian Academy of Sciences; State Novosibirsk Regional Clinical Hospital; Novosibirsk State Medical UniversityRussian Federation202626082026305824829Copyright © Кожевникова О.С., Никулич И.В., Дербенёва А.С., Девяткин В.А., Колоcова Н.Г., Фурсова А.Ж., 20262026Кожевникова О.С., Никулич И.В., Дербенёва А.С., Девяткин В.А., Колоcова Н.Г., Фурсова А.Ж.Kozhevnikova O.S., Nikulich I.F., Derbeneva A.S., Devyatkin V.A., Kolosova N..., Fursova А.Z.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://vavilov.elpub.ru/jour/article/view/5236

Возрастная макулярная дегенерация (ВМД) – прогрессирующее нейродегенеративное заболевание сетчатки, которое становится основной причиной снижения и потери зрения людьми старшего возраста. Аполипопротеин Е (АпоЕ) – один из ключевых белков липидного метаболизма, который экспрессируется в сетчатке и обнаруживается в друзах у пациентов с ВМД. Изоформы АпоЕ являются значимыми генетическими детерминантами риска ВМД (ε2 > ε3 > ε4), при этом эффекты аллелей APOE различаются в зависимости от этнической группы. Генотип APOE также может влиять на ответ на лечение. В данном исследовании мы оценили влияние аллелей APOE на риск неоваскулярной ВМД и ответ на анти-VEGF-терапию у пациентов из населения Западной Сибири. Генотипирование полиморфизмов rs429358 и rs7412 гена APOE проведено у пациентов с неоваскулярной ВМД (n = 315) и в контрольной группе (n = 317) с использованием аллель-специфической ПЦР. Для оценки связи аллелей APOE с ответом на лечение 275 пациентов были разделены на три группы по степени ответа на лечение (хороший, слабый, отсутствие ответа) после трех нагрузочных инъекций афлиберцепта. Мы выявили значимую ассоциацию между аллелем ε2 и неоваскулярной ВМД: у носителей ε2 риск развития ВМД был в 1.5 раза выше по сравнению с носителями других аллельных вариантов (ОШ = 1.536; 95 % ДИ: 1.075–2.195). Результаты указывают на умеренную связь аллеля ε2 с развитием неоваскулярной ВМД в российской популяции.

Однако не обнаружено ассоциации между генотипами APOE и краткосрочным ответом на анти-VEGF-терапию.

Age-related macular degeneration (AMD) is a progressive disease that leads to blindness and is the cause of visual impairment in an aging population. Apolipoprotein E (ApoE) is one of the key proteins in lipoprotein metabolism. ApoE is expressed in the retina and is found in drusen in AMD patients. ApoE isoforms are significant genetic determinants of AMD risk (ε2 > ε3 > ε4), wherein the effects of APOE alleles vary by ethnic group. APOE genotype may also influence response to treatment. Here we examine the effect of APOE alleles on the risk of neovascular AMD and response to anti-VEGF treatment in patients from the population of Western Siberia. Genotyping of the rs429358 and rs7412 polymorphisms of the APOE gene was carried out in patients with neovascular AMD (n = 315) and the control group (n = 317) using allele-specific PCR. To assess the association of APOE alleles with treatment response, 275 patients were categorized into three groups of treatment response (good, weak, no response) after three loading injections of aflibercept. We revealed a significant association between the ε2 allele and neovascular AMD: carriers of ε2 had a 1.5- fold higher risk of AMD compared with carriers of other allelic variants (OR = 1.536; 95% CI: 1.075–2.195). The results indicate a moderate association of the ε2 allele with the development of neovascular AMD in the Russian population. However, no association was found between APOE genotype and short-term response to anti-VEGF therapy. 

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