Russian Journal of GeneticsRussian Journal of GeneticsГенетика0016-67583034-5103The Russian Academy of Sciences66720210.31857/S0016675824090083adlxnvГЕНЕТИКА ЧЕЛОВЕКАResearch ArticlePolymorphic variants of long non-coding RNA genes in the development of type 2 diabetes mellitusПолиморфные варианты генов длинных некодирующих РНК в развитии сахарного диабета 2-го типаKochetovaO. V.КочетоваО. В.
Russian Federation

Institute of Biochemisrty and Genetics

институт биохимии и генетики

Olga_MK78@mail.ruAvzaleydinivaD. S.АвзалетдиноваД. Ш.
Russian Federation
Olga_MK78@mail.ruKochetovaT. M.КочетоваТ. М.
Russian Federation
Olga_MK78@mail.ruViktorovaT. V.ВиктороваТ. В.
Russian Federation
Olga_MK78@mail.ruKorytinaG. F.КорытинаГ. Ф.
Russian Federation

Institute of Biochemisrty and Genetics

институт биохимии и генетики

Olga_MK78@mail.ruUfa Scientific Center of the Russian Academy of SciencesУфимский федеральный исследовательский центр Российской академии наукBashkir State Medical UniversityБашкирский государственный медицинский университет10092024609637326022025Copyright ©; 2024, Russian Academy of SciencesCopyright ©; 2024, Российская академия наук2024Russian Academy of SciencesРоссийская академия наукhttps://transsyst.ru/0016-6758/article/view/667202

Type 2 diabetes mellitus (T2DM) is a disease characterized by increased blood glucose, formed as a result of impaired mechanisms of insulin binding to cells. DNA samples of patients with T2DM (N = 535) and healthy individuals (N = 475) were used. We identified the association of lncRNA gene loci LINC02227 rs2149954 (OR = 0.76, P = 0.0083, PFDR = 0.017), LINC00305 rs2850711 (OR = 1.43, P = 0.0017, PFDR = 0.004) and CDKN2B-AS1 rs4977574 (OR = 0.70, P = 0.0001, PFDR = 0.0003) in an additive model with T2DM. The LINC00305 gene locus rs2850711 showed association with fasting glucose level (P = 0.023), C-peptide level (P = 0.00001), LINC02227 rs2149954 and CDKN2B-AS1 rs4977574 loci showed association with hypertension. MALAT rs619586 gene polymorphism was associated with C-peptide (P = 0.017), LDL (P = 0.012) and total cholesterol levels (P = 0.01). CDKN2B-AS1 rs4977574 gene polymorphism showed association with C-peptide levels (P = 0.027). SNP LINC02227 rs2149954 was associated with obesity (P = 0.0011, PFDR = 0.008). MEG3 rs7158663 gene polymorphism was associated with post infarct cardiosclerosis (P = 0.02). ROC curve analysis showed that the studied loci and variables such as sex, age of subjects and BMI level, included in the construction of the risk calculation model, could predict the development of T2DM with a sensitivity of 98.0% and specificity of 97.0%, the area under the AUC curve was 95.30% (95%CI 93.50–97.40).

Сахарный диабет 2-го типа (СД2) – это заболевание, характеризующееся повышенным содержанием глюкозы в крови, формирующееся в результате нарушения механизмов связывания инсулина с клетками. Использовали образцы ДНК больных (N = 535) и здоровых (N = 475) индивидов. Нами выявлена ассоциация с риском развития СД2-локусов генов днРНК в аддитивной модели LINC02227 rs2149954 (OR = 0.76, Р = 0.0083, PFDR = 0.017), LINC00305 rs2850711 (OR = 1.43, Р = 0.0017, PFDR = 0.004) и CDKN2B-AS1 rs4977574 (OR = 0.70, Р = 0.0001, PFDR = 0.0003). Для локуса rs2850711 гена LINC00305 выявлена ассоциация с уровнем глюкозы натощак (Р = 0.023), уровнем С-пептида (Р = 0.00001), для локусов LINC02227 rs2149954 и CDKN2B-AS1 rs4977574 установлена ассоциация с гипертонией. Локус MALAT rs619586, аллель А ассоциирован с повышенным уровнем С-пептида (Р = 0.017), с ЛПНП (Р = 0.012) и общим холестерином (Р = 0.01). Для локуса CDKN2B-AS1 rs4977574 показана ассоциация с уровнем С-пептида (Р = 0.027). Локус LINC02227 rs2149954 (Р = 0.0011, PFDR = 0.008) ассоциирован с развитием ожирения. Локус rs7158663 гена MEG3 ассоциирован с постинфарктным кардиосклерозом (Р = 0.02). Проведенный анализ ROC-кривых показал, что исследуемые локусы MEG3 rs7158663, H19 rs3741219, MALAT rs619586, LINC02227 rs2149954, LINC00305 rs2850711, CDKN2B-AS1 rs4977574 и такие переменные, как пол, возраст обследуемых и уровень ИМТ, включенные в построение модели расчета риска, могут предсказывать развитие СД2 с чувствительностью 98.0% и специфичностью 97.0%, площадь под кривой AUC составила 95.30% (95%CI 93.50–97.40).

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