Ecological geneticsEcological geneticsЭкологическая генетика1811-09322411-9202Eco-Vector1629310.17816/ecogen16293Human ecological geneticsЭкологическая генетика человекаResearch ArticleGenetic and biochemical investigation of the gamma-glutamylcyclotransferase role in predisposition to type 2 diabetes mellitusГенетико-биохимическое исследование роли гамма-глутамилциклотрансферазы в формировании предрасположенности к сахарному диабету 2-го типаhttps://orcid.org/0000-0001-8098-805257200117409S-7266-20189173-3698AzarovaIuliia E.АзароваЮлия Эдуардовна
Russian Federation

MD, PhD, Associate Professor of Department of Biological Chemistry of KSMU, Head of Laboratory of Biochemical Genetics and Metabolomics of Research Institute for Genetic and Molecular Epidemiology

канд. мед. наук, доцент кафедры биологической химии, зав. лабораторией биохимической генетики и метаболомики НИИ генетической и молекулярной эпидемиологии

azzzzar@yandex.ruhttps://orcid.org/0000-0002-1543-92305121-7160KlyosovaElena Yu.КлёсоваЕлена Юрьевна
Russian Federation

Biotechnologist of the Laboratory of Biochemical Genetics and Metabolomics of Research Institute of Genetic and Molecular Epidemiology of KSMU

Биотехнолог лаборатории биохимической генетики и метаболомики НИИ генетической и молекулярной эпидемиологии КГМУ

ecless@yandex.ruhttps://orcid.org/0000-0002-6064-986X7796067728-6220ChurilinMikhail I.ЧурилинМихаил Иванович
Russian Federation

Assistant Lecturer of Department of Infectious Diseases

ассистент, кафедра инфекционных болезней и эпидемиологии

mpmi2@yandex.ruhttps://orcid.org/0000-0002-7781-37939973-9738SamginaTatiana A.СамгинаТатьяна Александровна
Russian Federation

MD, PhD, Associate Professor, Associate Professor of Department of Surgical Diseases No. 2

канд. мед. наук, доцент, доцент кафедры хирургических болезней № 2

tass@list.ruhttps://orcid.org/0000-0003-4748-84056602518934H-2197-20139631-2390KonoplyaAlexander I.КонопляАлександр Иванович
Russian Federation

MD, PhD, Professor, Professor of Department of Biological Chemistry

д-р мед. наук, профессор, профессор кафедры биологической химии

konoplya51@mail.ruhttps://orcid.org/0000-0001-6280-247X6506508435R-7537-20166373-6556PolonikovAlexey V.ПолониковАлексей Валерьевич
Russian Federation

MD, PhD, Professor, Professor of Department of Biology, Medical Genetics and Ecology, Head of Laboratory of Statistical Genetics and Bioinformatics of Research Institute for Genetic and Molecular Epidemiology

д-р мед. наук, профессор, профессор кафедры биологии, медицинской генетики и экологии, зав. лабораторией статистической генетики и биоинформатики, НИИ генетической и молекулярной эпидемиологии

polonikov@rambler.ruKursk State Medical UniversityФедеральное государственное бюджетное образовательное учреждение высшего образования «Курский государственный медицинский университет» Министерства здравоохранения Российской Федерации14042020080720201822152282709201905022020Copyright ©; 2020, Azarova I.E., Klyosova E.Y., Churilin M.I., Samgina T.A., Konoplya A.I., Polonikov A.V.Copyright ©; 2020, Азарова Ю.Э., Клёсова Е.Ю., Чурилин М.И., Самгина Т.А., Конопля А.И., Полоников А.В.2020Azarova I.E., Klyosova E.Y., Churilin M.I., Samgina T.A., Konoplya A.I., Polonikov A.V.Азарова Ю.Э., Клёсова Е.Ю., Чурилин М.И., Самгина Т.А., Конопля А.И., Полоников А.В.http://creativecommons.org/licenses/by/4.0https://journals.eco-vector.com/ecolgenet/article/view/16293

Background. Imbalance in the system of redox homeostasis is an important link in the pathogenesis of type 2 diabetes (T2D). Gamma-glutamyl cyclotransferase is an antioxidant defense enzyme directly involved in the metabolism of glutathione, an endogenous antioxidant.

The aim of the study was to examine the association of single nucleotide polymorphisms (SNP) rs38420 (G > A), rs4270 (T > C), rs6462210 (C > T) and rs28679 (G > A) in GGCT gene with the risk of developing T2D.

Materials and Methods. The study included 1022 T2D patients and 1064 healthy volunteers. Genotyping of GGCT gene loci was performed using iPLEX technology on a MassARRAY Analyzer 4 genome time-of-flight mass spectrometer (Agena Bioscience).

Results. As a result, we identified for the first time the association of SNP rs4270 in the GGCT gene with the risk of T2D in the Russian population. We have also established genetic and environmental interactions associated with predisposition to the disease: protective effect of gamma-glutamyl cyclotransferase gene was observed only in non-smokers under condition of daily consumption of fresh vegetables and fruits, whereas in persons with insufficient consumption of plant foods, as well as in all smoking patients protective effect of GGCT was not observed. In patients with T2D, the level of hydrogen peroxide and glutathione monomer was sharply increased compared to the controls. SNP rs4270 was also found to be associated with elevated levels of reduced glutathione in the plasma of type 2 diabetics.

Conclusion. Thus, for the first time it was established that polymorphic locus rs4270 in the GGCT gene is associated with a predisposition to T2D, but its relationship with the disease is modulated by smoking and fresh plant foods consumption.

Дисбаланс в системе редокс-гомеостаза является важным звеном патогенеза сахарного диабета 2-го типа (СД2). Гамма-глутамилциклотрансфераза представляет собой фермент антиоксидантной защиты, непосредственно вовлеченный в метаболизм глутатиона, эндогенного антиоксиданта. Целью исследования стало изучение ассоциации однонуклеотидных замен (SNP) rs38420 (G > A), rs4270 (T > C), rs6462210 (C > T) и rs28679 (G > A) в гене GGCT с СД2. В исследование включено 1022 пациента с СД2 и 1064 условно здоровых добровольца. В результате нами впервые выявлена взаимосвязь SNP rs4270 гена GGCT с СД2 в русской популяции. Нами также установлены генно-средовые взаимодействия, ассоциированные с предрасположенностью к заболеванию: протективный эффект гена гамма-глутамилциклотрансферазы проявлялся только у некурящих лиц при условии ежедневного употребления ими свежих овощей и фруктов, тогда как у лиц с недостаточным потреблением растительной пищи, а также у всех курящих больных защитный эффект GGCT не наблюдался. У пациентов с СД2 содержание перекиси водорода и мономера глутатиона резко повышено по сравнению с контролем. Также было установлено, что SNP rs4270 связан с повышенным содержанием восстановленного глутатиона в плазме крови больных СД2. Таким образом, впервые установлено, что полиморфный локус rs4270 в гене GGCT ассоциирован с предрасположенностью к СД2, но его связь с заболеванием модулируется курением и употреблением свежей растительной пищи.

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