diaendoСахарный диабетDiabetes mellitus2072-03512072-0378Endocrinology research centre10.14341/DM12767diaendo-12767Research ArticleОригинальные исследованияOriginal StudiesАссоциация полиморфизмов генов SLC30A8 и MC4R с прогнозом развития сахарного диабета 2-го типаAssociation of polymorphisms of genes SLC30A8 and MC4R with the prognosis of the development of type 2 diabetes mellitushttps://orcid.org/0000-0002-9033-1588МельниковаЕ. С.Mel’nikovaE. S.

Мельникова Елизавета Сергеевна, аспирант

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

Scopus Author ID: 57221300480;

eLibrary SPIN: 3319-8546

Elizaveta S. Mel’nikova; MD, PhD student

175/1, Borisa Bogatkova str., 630089 Novosibirsk

Scopus Author ID: 57221300480;

eLibrary SPIN: 3319-8546

jarinaleksi@list.ruhttps://orcid.org/0000-0002-7165-4496МустафинаС. В.MustafinaS. V.

Мустафина Светлана Владимировна, доктор медицинских наук

Новосибирск

Researcher ID: Q-9286-2017;

Scopus Author ID: 24339090600;

eLibrary SPIN: 8395-1395

Svetlana V. Mustafina, MD, PhD

Новосибирск

Researcher ID: Q-9286-2017;

Scopus Author ID: 24339090600;

eLibrary SPIN: 8395-1395

medik11@mail.ruhttps://orcid.org/0000-0003-4095-0169РымарО. Д.RymarO. D.

Рымар Оксана Дмитриевна, доктор медицинских наук

Новосибирск

Scopus Author ID: 24339174300;

eLibrary SPIN: 8345-9365

Oksana D. Rymar, MD, PhD

Novosibirsk

Scopus Author ID: 24339174300;

eLibrary SPIN: 8345-9365

orymar23@gmail.comhttps://orcid.org/0000-0002-9460-6294ИвановаА. А.IvanovaA. A.

Иванова Анастасия Андреевна, кандидат медицинских наук

Новосибирск

Researcher ID: O-2341-2017;

Scopus Author ID: 571896

Anastasiia A. Ivanova, MD, PhD

Novosibirsk

Researcher ID: O-2341-2017;

Scopus Author ID: 571896

ivanova_a_a@mail.ruhttps://orcid.org/0000-0001-9270-9188ЩербаковаЛ. В.ShcherbakovaL. V.

Щербакова Лилия Валерьевна

Новосибирск

eLibrary SPIN: 5849-7040

Liliya V. Shcherbakova

Novosibirsk

eLibrary SPIN: 5849-7040

9584792@mail.ruhttps://orcid.org/0000-0002-2633-6851БобакМ.BobakM.

Бобак Мартин, доктор медицинских наук, профессор

Лондон

Martin Bobak, MD, PhD, Professor

London

m.bobak@ucl.ac.ukhttps://orcid.org/0000-0001-6539-0466МалютинаС. К.MaljutinaS. K.

Малютина Софья Константиновна, доктор медицинских наук, профессор

Новосибирск

Scopus Author ID: 57221302312;

eLibrary SPIN: 6780-9141

Sofia K. Maliutina, MD, PhD, Professor

Novosibirsk

Scopus Author ID: 57221302312;

eLibrary SPIN: 6780-9141

smalyutina@hotmail.comhttps://orcid.org/0000-0001-9425-413XВоеводаМ. И.VoevodaM. I.

Воевода Михаил Иванович, доктор медицинских наук, профессор, академик РАН

Новосибирск

Researcher ID: N-6713-2015;

Scopus Author ID: 57195959148;

eLibrary SPIN: 6133-1780

Mihail I. Voevoda, MD, PhD, Professor, academician RAS

Novosibirsk

Researcher ID: N-6713-2015;

Scopus Author ID: 57195959148;

eLibrary SPIN: 6133-1780

mvoevoda@ya.ruhttps://orcid.org/0000-0002-7165-4496МаксимовВ. Н.MaksimovV. N.

Максимов Владимир Николаевич, доктор медицинских наук, профессор

Новосибирск

Researcher ID: H-7676-2012;

Scopus Author ID: 7202540327;

eLibrary SPIN: 9953-7867

Vladimir N. Maksimov, MD, PhD, Professor

Novosibirsk

Researcher ID: H-7676-2012;

Scopus Author ID: 7202540327;

eLibrary SPIN: 9953-7867

medik11@mail.ruНаучно-исследовательский институт терапии и профилактической медицины – филиал ФГБНУ «Федеральный исследовательский центр Институт цитологии и генетики» Сибирского отделения РАНРоссияResearch Institute of Internal and Preventive Medicine — Branch of the Institute of Cytology and GeneticsRussian FederationНаучно-исследовательский институт терапии и профилактической медицины — филиал «Федеральный исследовательский центр Институт цитологии и генетики» Сибирского отделения РАНРоссияResearch Institute of Internal and Preventive Medicine — Branch of the Institute of Cytology and GeneticsRussian FederationУниверситетский колледж ЛондонаВеликобританияUniversity College LondonUnited Kingdom202205062022253215225Copyright © Мельникова Е.С., Мустафина С.В., Рымар О.Д., Иванова А.А., Щербакова Л.В., Бобак М., Малютина С.К., Воевода М.И., Максимов В.Н., 20222022Мельникова Е.С., Мустафина С.В., Рымар О.Д., Иванова А.А., Щербакова Л.В., Бобак М., Малютина С.К., Воевода М.И., Максимов В.Н.Mel’nikova E.S., Mustafina S.V., Rymar O.D., Ivanova A.A., Shcherbakova L.V., Bobak M., Maljutina S.K., Voevoda M.I., Maksimov V.N.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.dia-endojournals.ru/jour/article/view/12767ОБОСНОВАНИЕ

ОБОСНОВАНИЕ. Распространенность сахарного диабета 2 типа (СД2) достигла масштабов эпидемии — более 400 млн человек во всем мире. Ожидается, что заболеваемость СД2 будет продолжать расти и, согласно прогнозам, к 2050 г. затронет почти каждого третьего человека. Эти тревожные прогнозы указывают на острую необходимость разработки и внедрения новых стратегий профилактики и лечения для борьбы с ростом распространенности СД2.

ЦЕЛЬ

ЦЕЛЬ. Изучить возможность использования в популяции г. Новосибирска в качестве маркеров прогноза развития СД2 полиморфизмов гена SLC30A8, кодирующего трансмембранный белок-транспортер ионов цинка типа 8 и гена рецептора меланокортина-4 (MC4R).

МАТЕРИАЛЫ И МЕТОДЫ

МАТЕРИАЛЫ И МЕТОДЫ. На основе проспективного наблюдения репрезентативной популяционной выборки жителей Новосибирска (The HAPIEE Project) сформированы 2 группы по принципу «случай–контроль» (случай — лица, у которых за 10 лет наблюдения выявлен СД2, и контроль — лица, у которых за 10-летний период не развились нарушения углеводного обмена). Группа СД2 — (n=443, средний возраст 56,2±6,7 года, мужчины — 29,6%, группа контроля — n=532, средний возраст 56,1±7,1 года, мужчины — 32,7%. ДНК выделена методом фенол-хлороформной экстракции. Генотипирование выполнено методом полимеразной цепной реакции с последующим анализом полиморфизма длин рестрикционных фрагментов. Статистическая обработка проведена с использованием программного пакета SPSS 16.0.

РЕЗУЛЬТАТЫ

РЕЗУЛЬТАТЫ. Гомозиготный генотип ТТ rs13266634 гена SLC30A8 является генотипом риска развития СД2 у женщин всех возрастных групп (относительный риск — ОР 1,51; 95% доверительный интервал — ДИ 1,11–2,05, р=0,008). Генотип СС rs13266634 гена SLC30A8 ассоциирован с протективным эффектом в отношении СД2 (ОР 0,57; 95% ДИ 0,35–0,92; р=0,026). Не обнаружено значимого влияния rs17782313 гена MC4R на риск развития СД2.

ЗАКЛЮЧЕНИЕ

ЗАКЛЮЧЕНИЕ. Полиморфизм rs13266634 гена SLC30A8 подтвердил свою ассоциацию с прогнозом развития СД2, что указывает на возможность его рассмотрения в качестве кандидата на внесение в рискометр СД2. Ассоциация с прогнозом развития СД2 полиморфизма rs17782313 гена MC4R не обнаружена.

BACKGROUND

BACKGROUND: The prevalence of Type 2 diabetes mellitus (T2DM) has reached epidemic proportions and it is estimated to affect over 400 million people worldwide. Moreover, the incidence of diabetes is expected to continue to rise and it is projected to affect nearly one of the three individuals by the year 2050. These alarming projections suggest that there is an urgent need for the development and implementation of novel prevention and treatment strategies to combat the rise in T2DM.

AIM

AIM: To study the possibility of using polymorphisms of genes SLC30A8 and MC4R as markers for predicting the development of T2D in the population of Novosibirsk.

MATERIALS AND METHODS

MATERIALS AND METHODS: On the basis of prospective follow-up of a representative population sample of residents of Novosibirsk (The HAPIEE Project), 2 groups were formed according to the “case-control” principle (case — people who had diabetes mellitus 2 over 10 years of follow-up, and control — people who did not developed disorders of carbohydrate metabolism). T2D group (n = 443, mean age 56.2 ± 6.7 years, men — 29.6%, women — 70.4%), control group (n = 532, mean age 56.1 ± 7.1 years, men — 32.7%, women — 67.3%). DNA was isolated by phenol-chloroform extraction. Genotyping was performed by the method of polymerase chain reaction with subsequent analysis of restriction fragment length polymorphism, polymerase chain reaction in real time. Statistical processing was carried out using the SPSS 16.0 software package.

RESULTS

RESULTS: Genotype TT rs13266634 of the SLC30A8 gene was associated with the risk of developing T2D (relative risk — RR 1.51, 95% confidence interval — CI 1.11–2.05, p =0.008). The CC genotype rs13266634 of the SLC30A8 gene was associated with a protective effect against T2D (RR 0.57, 95% CI 0.35–0.92, p=0.026). No significant effect of rs17782313 of the MC4R gene on the risk of developing T2D was found.

CONCLUSION

CONCLUSION: The rs13266634 polymorphism of the SLC30A8 gene confirmed its association with the prognosis of the development of T2D, which indicates the possibility of considering it as a candidate for inclusion in a diabetes risk score. The association between polymorphisms rs17782313 of the MC4R gene and the prognosis of the development of T2D was not found.

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