2658-6533Научные результаты биомедицинских исследований2658-653310.18413/2658-6533-2023-9-4-0-33245Генетика<strong>Связь однонуклеотидного полиморфизма rs4880 гена </strong><em><strong>SOD2</strong></em><strong> с развитием микрососудистых осложнений сахарного диабета 2-го типа</strong><strong>The link of single nucleotide polymorphism rs4880 of the <em>SOD2</em> gene to the development of microvascular complications of type 2 diabetes mellitus</strong>АзароваЮлия ЭдуардовнаAzarovaIuliia E.azzzzar@yandex.ruГурееваАнастасия ВладимировнаGureevaAnastasia V.nastasyi.207@gmail.comПостниковаМария ИгоревнаPostnikovaMariia I.postnikova0700@icloud.comМакаренкоВиктор ВикторовичMakarenkoVictor V.vm200046@gmail.comКлёсоваЕлена ЮрьевнаKlyosovaElena Yu.ecless@yandex.ruПолониковАлексей ВалерьевичPolonikovAlexei V.polonikov@rambler.ru20239400

Актуальность: Ген супероксиддисмутазы 2 (SOD2) кодирует митохондриальный фермент, главной функцией которого является превращение супероксид-аниона в перекись водорода. Генетически детерминированное снижение активности фермента SOD2 в случае однонуклеотидной замены rs4880 (А&gt;G) может способствовать развитию нарушения редокс-баланса митохондрий бета-клеток поджелудочной железы и других тканей, имеющих патогенетическое значение для возникновения сахарного диабета 2 типа (СД2) и его микрососудистых осложнений. Цель исследования: Провести анализ ассоциаций миссенс-варианта rs4880 SOD2, приводящего к замене валина на аланин в белковом продукте гена, с риском развития СД2 и его микрососудистых осложнений &ndash; диабетической ретинопатии (ДР) и нефропатии (ДНФ). Материалы и методы: В исследование включено 3206 человек, жителей Центральной России, у 1579 из которых диагностирован СД2. При этом у 991 пациента с СД2 установлено наличие ДР, у 544 больных СД2 выявлена ДНФ. Генотипирование выполнено методом полимеразно-цепной реакции в реальном режиме времени на термоциклере CFX1000 Bio-Rad с использованием TaqMan зондов. Статистический анализ ассоциаций выполнен с помощью онлайн программы SNPStats. Результаты: Установлена ассоциация минорного аллеля G (OR=1,26, 95% CI=1,02-1,56, P=0,033), а также генотипов А/G и G/G rs4880 (OR=1,51, 95% CI=1,09-2,11, P=0,015) c риском развития ДР у больных СД2 женщин. Статистически значимых ассоциаций rs4880 с СД2 и с развитием ДНФ ни у мужчин, ни у женщин выявлено не было: Р&gt;0.05. По данным транскриптомного анализа поджелудочной железы, нервной и сосудистой тканей (GTEx Portal), вариантный аллель G связан со снижением экспрессии белка MRPL18, необходимого для транспортировки важнейшего компонента рибосом 5S рРНК из цитозоля в митохондрии и обеспечения рибосомального синтеза белка. Заключение: Носительство минорного аллеля rs4880-G является генетическим маркером повышенного риска развития диабетической ретинопатии у женщин с СД2

Background: The superoxide dismutase 2 (SOD2) gene encodes a mitochondrial enzyme whose main function is to convert superoxide anion to hydrogen peroxide. A genetically determined decrease in the activity of the SOD2 enzyme in the case of a single nucleotide variant rs4880 (A&gt;G) may contribute to the development of redox imbalance in the mitochondria of beta cells of the pancreas and other tissues, which have pathogenic significance in the occurrence of type 2 diabetes mellitus (T2DM) and its microvascular complications. The aim of the study: To analyze the association of the missense variant rs4880 SOD2, leading to the replacement of valine with alanine in the protein product of the gene, with the risk of developing T2D and its microvascular complications &ndash; diabetic retinopathy (DR) and nephropathy (DNF). Materials and methods: The study included 3206 subjects, residents of Central Russia, 1579 of whom were diagnosed with T2D. At the same time, DR was detected in 991 patients with T2D, and DNF was detected in 544 patients with T2D. Genotyping was performed by real-time polymerase chain reaction on a Bio-Rad CFX1000 thermal cycler using TaqMan probes. Statistical analysis of associations was performed using the SNPStats online program. Results: An association was established for the minor allele G (OR=1.26, 95% CI=1.02-1.56, P=0.033), as well as genotypes A/G and G/G rs4880 (OR=1.51, 95% CI=1.09-2.11, P=0.015) with a risk of developing DR in females with T2D. No statistically significant associations with T2D and the development of DNF were identified: P&gt;0.05. Conclusion: Carriage of the minor allele rs4880-G is a genetic marker of an increased risk of developing diabetic retinopathy in females with T2D.

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