aterosklerozАтеросклерозAteroscleroz2078-256X2949-3633НИИТПМ-филиал ИЦиГ СО РАН10.52727/2078-256X-2023-19-1-6-18ateroskleroz-885Research ArticleОРИГИНАЛЬНЫЕ СТАТЬИORIGINAL ARTICLESАнализ ассоциации вариантов генов аполипопротеинов APOA2, APOA5 и APOH с гиперлипидемиейAnalysis of association of apolipoprotein genes APOA2, APOA5 and APOH variants with hyperlipidemiahttps://orcid.org/0000-0002-0897-5473МихайловаС. В.MikhailovaS. V.

Светлана Владимировна Михайлова, канд. биол. наук, научный сотрудник, исполняющая обязанности зав. лабораторией молекулярной генетики человека

630090, г. Новосибирск, просп. Академика Лаврентьева, 10

Svetlana V. Mikhailova, candidate of biological sciences, head of the laboratory of human molecular genetics

10, Academician Lavrentiev av., Novosibirsk, 630090

https://orcid.org/0000-0002-0403-545XИванощукД. Е.IvanoshchukD. E.

Динара Евгеньевна Иванощук, младший научный сотрудник лаборатории молекулярной генетики человека; научный сотрудник лаборатории молекулярно-генетических исследований терапевтических заболеваний

630090, г. Новосибирск, просп. Академика Лаврентьева, 10

630089, г. Новосибирск, ул. Бориса Богаткова, 175/1

Dinara E. Ivanoshchuk, junior researcher at the laboratory of human molecular genetics, Institute of Cytology and Genetics; researcher in the laboratory of the molecular genetic investigations of the therapeutic diseases

10, Academician Lavrentiev av., Novosibirsk, 630090

175/1, Boris Bogatkov str., Novosibirsk, 630089

dinara2084@mail.ruhttps://orcid.org/0000-0002-8828-0259ШироковаН. С.ShirokovaN. S.

Нина Сергеевна Широкова, студент

630090, г. Новосибирск, ул. Пирогова, 1

Nina S. Shirokova, student

1, Pirogov str., Novosibirsk, 630090

https://orcid.org/0000-0001-9371-2178ОрловП. С.OrlovP. S.

Павел Сергеевич Орлов, младший научный сотрудник лаборатории молекулярной генетики человека; научный сотрудник лаборатории молекулярно-генетических исследований терапевтических заболеваний

630090, г. Новосибирск, просп. Академика Лаврентьева, 10

630089, г. Новосибирск, ул. Бориса Богаткова, 175/1

Pavel S. Orlov, junior researcher at the laboratory of human molecular genetics, Institute of Cytology and Genetics; researcher in the laboratory of the molecular genetic investigations of the therapeutic diseases

10, Academician Lavrentiev av., Novosibirsk, 630090

175/1, Boris Bogatkov str., Novosibirsk, 630089

orlovpavel186@gmail.comhttps://orcid.org/0000-0001-7127-7793БейркдарА.BairqdarA.

Ахмад Бейркдар, младший научный сотрудник сектора изучения моногенных форм распространенных заболеваний человека; аспирант

630090, г. Новосибирск, просп. Академика Лаврентьева, 10

630090, г. Новосибирск, ул. Пирогова, 1

Аhmad Bairqdar, junior researcher at the division of monogenic forms of human common disease, Institute of Cytology and Genetics; Phd student

10, Academician Lavrentiev av., Novosibirsk, 630090

1, Pirogov str., Novosibirsk, 630090

https://orcid.org/0000-0001-6108-1025ШахтшнейдерЕ. В.ShachtshneiderE. V.

Елена Владимировна Шахтшнейдер, канд. мед. наук, ведущий научный сотрудник, зав. сектором изучения моногенных форм распространенных заболеваний человека; зам. руководителя по научной работе, ведущий научный сотрудник лаборатории молекулярно-генетических исследований  терапевтических заболеваний

630090, г. Новосибирск, просп. Академика Лаврентьева, 10

630089, г. Новосибирск, ул. Бориса Богаткова, 175/1

Elena V. Shakhtshneider, candidate of medical sciences, MD, leading researcher, head of the division of monogenic forms of human common Disease, Institute of Cytology and Genetics; leader researcher in the laboratory of the molecular genetic investigations of therapeutic diseases

10, Academician Lavrentiev av., Novosibirsk, 630090

175/1, Boris Bogatkov str., Novosibirsk, 630089

Федеральное государственное бюджетное научное учреждение «Федеральный исследовательский центр Институт цитологии и генетики Сибирского отделения Российской академии наук»РоссияFederal Research Center Institute of Cytology and Genetics of Siberian Branch of the Russian Academy of SciencesRussian FederationФедеральное государственное бюджетное научное учреждение «Федеральный исследовательский центр Институт цитологии и генетики Сибирского отделения Российской академии наук»; Научно-исследовательский институт терапии и профилактической медицины – филиал Федерального государственного бюджетного научного учреждения «Федеральный исследовательский центр Институт цитологии и генетики Сибирского отделения Российской академии наук»РоссияFederal Research Center Institute of Cytology and Genetics of Siberian Branch of the Russian Academy of Sciences; Research Institute of Internal and Preventive Medicine – Branch of Federal Research Center Institute of Cytology and Genetics of Siberian Branch of the Russian Academy of SciencesRussian FederationФедеральное государственное автономное образовательное учреждение высшего образования «Новосибирский национальный исследовательский государственный университет»РоссияNovosibirsk State UniversityRussian FederationФедеральное государственное бюджетное научное учреждение «Федеральный исследовательский центр Институт цитологии и генетики Сибирского отделения Российской академии наук»; Федеральное государственное автономное образовательное учреждение высшего образования «Новосибирский национальный исследовательский государственный университет»РоссияFederal Research Center Institute of Cytology and Genetics of Siberian Branch of the Russian Academy of Sciences; Novosibirsk State UniversityRussian Federation202304042023191618Copyright © Михайлова С.В., Иванощук Д.Е., Широкова Н.С., Орлов П.С., Бейркдар А., Шахтшнейдер Е.В., 20232023Михайлова С.В., Иванощук Д.Е., Широкова Н.С., Орлов П.С., Бейркдар А., Шахтшнейдер Е.В.Mikhailova S.V., Ivanoshchuk D.E., Shirokova N.S., Orlov P.S., Bairqdar A., Shachtshneider E.V.This work is licensed under a Creative Commons Attribution 4.0 License.https://ateroskleroz.elpub.ru/jour/article/view/885

Гиперлипидемия – одно из самых распространенных нарушений метаболизма у человека, в случае несвоевременной диагностики и отсутствии терапии приводящее к развитию атеросклероза. Известно, что нарушения обмена липидов могут быть связаны не только с образом жизни, но и с генетической предрасположенностью. Однако даже у пациентов с клинически подтвержденной семейной гиперхолестеринемией ее генетическая причина остается неизвестной в 30 % случаев. Поиск генетических вариантов, ассоциированных с гиперлипидемиями, является перспективным направлением развития диагностики и методов персонализированной медицины. Цель исследования – оценка ассоциации полиморфных сайтов rs3813627, rs3135506 и rs3785617 генов аполипопротеинов APOA2, APOA5 и APOH соответственно с показателями липидного обмена и индексом атерогенности в популяции г. Новосибирска. Материал и методы. Проведено генотипирование методом ПЦР с последующим анализом полиморфизма длин рестрикционных фрагментов ДНК по полиморфным сайтам rs3813627, rs3135506 и rs3785617 у 522 человек из случайной выборки 9360 человек населения г. Новосибирска и у 266 человек из этой же основной выборки с уровнем общего холестерина более 300 мг/дл. Выполнен однофакторный дисперсионный анализ ассоциации генетических вариантов c уровнем липидов крови и индексом атерогенности. Результаты. Частоты аллелей всех изученных полиморфных сайтов в популяционной выборке г. Новосибирска отличались от выявленных ранее в Европейских популяциях. Обнаружено увеличение концентрации общего холестерина в ряду генотипов AA – AG – GG по rs3785617 гена APOH (p = 0,02). Частота генотипа СС rs3135506 гена APOA5 в выборке населения с содержанием общего холестерина, превышающим 300 мг/дл, была меньше (p = 0,038, отношение шансов 0,66, 95%-й доверительный интервал 0,46–0,97), чем в контрольной группе. Для rs3813627 различий в частотах генотипов между выборками, а также в показателях липидного обмена у носителей разных генотипов не выявлено. Заключение. Варианты rs3135506 и rs3785617 могут модифицировать фенотип гиперлипидемии у европеоидного населения Западной Сибири.

Hyperlipidemia is one of the most common metabolic disorders in humans, leading to the atheros clerosis. It is known that lipid metabolism disorders can be associated with genetic predisposition. However, even in patients with clinically confirmed familial hypercholesterolemia, its genetic cause remains unknown in 30 % of cases. The search for genetic variants associated with primary hyperlipidemias is a promising direction in the development of diagnostics and personalized medicine. Aim of the study was to assess of the association of polymorphic sites rs3813627, rs3135506 and rs3785617 of the apolipoprotein genes APOA2, APOA5 and APOH, respectively, with lipid metabolism and atherogenic index in the population of Novosibirsk. Material and methods. Genotyping by polymerase chain reaction followed by analysis of restriction fragment length polymorphism at the rs3813627, rs3135506 and rs3785617 of the APOA2, APOA5 and APOH genes, respectively, was carried out in 522 people from 9360 a random population sample of Novosibirsk and in 266 people from the same sample with a total cholesterol content more than 300 mg/dl. A one-way ANOVA of the association of genetic variants with serum lipid levels and atherogenicity index was performed. Results. The allele frequencies of all studied polymorphic sites in the Novosibirsk population differed from those previously identified among Europeans. A significant increase (p = 0.02) in average total cholesterol content in AA – AG – GG genotype series for rs3785617 of the APOH was revealed. The frequency of the CC genotype for the rs3135506 of the APOA5 in the group with total cholesterol contentration exceeding 300 mg/dl was lower compared to the control group (p = 0.038, odds ratio 0.66, 95 % confidence interval 0.46–0.97). For rs3813627, there were no differences in genotype frequencies and in lipid metabolism. Conclusions. The rs3135506 and rs3785617 can modify the hyperlipidemia phenotype among the Caucasoid population of Western Siberia.

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