docruДоктор.РуTitle1727-23782713-2994ООО "ГК "РУСМЕДИКАЛ"10.31550/1727-2378-OF2.25_Adocru-342Research ArticleОРИГИНАЛЬНЫЕ СТАТЬИORIGINAL PAPERSАссоциация нуклеотидной последовательности rs3730089 гена PIK3R1 с дислипидемией при сахарном диабете 1 типаAssociation of the rs3730089 Nucleotide Sequence of the PIK3R1 Gene with Dyslipidemia in Type 1 Diabetes Mellitushttps://orcid.org/0000-0001-9841-0611МалиевскаяР. И.MalievskayaR. I.

Малиевская Рамзия Илюсовна — ассистент кафедры эндокринологии

г. Уфа

Ufa

ramsiya1987@mail.ruhttps://orcid.org/0000-0002-1590-6433АвзалетдиноваД. Ш.AvzaletdinovaD. Sh.

Авзалетдинова Диана Шамилевна — д. м. н., профессор кафедры эндокринологии

г. Уфа

Ufa

hyppocrat@mail.ruhttps://orcid.org/0000-0003-2599-0867МалиевскийО. А.MalievskiyO. A.

Малиевский Олег Артурович — д. м. н., профессор кафедры госпитальной педиатрии

г. Уфа

Ufa

malievsky@list.ruhttps://orcid.org/0000-0003-2071-0969КочетоваО. В.KochetovaO. V.

Кочетова Ольга Владимировна — к. б. н., доцент кафедры биологии

г. Уфа

Ufa

olga_mk78@mail.ruФГБОУ ВО «Башкирский государственный медицинский университет» Минздрава РоссииРоссияBashkir State Medical UniversityRussian Federation202513112025244КАРДИОМЕТАБОЛИЧЕСКАЯ МЕДИЦИНА30–36Copyright © Малиевская Р.И., Авзалетдинова Д.Ш., Малиевский О.А., Кочетова О.В., 20252025Малиевская Р.И., Авзалетдинова Д.Ш., Малиевский О.А., Кочетова О.В.Malievskaya R.I., Avzaletdinova D.S., Malievskiy O.A., Kochetova O.V.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://docru.elpub.ru/jour/article/view/342Цель

Цель. Провести анализ ассоциации варианта нуклеотидной последовательности rs3730089 гена PIK3R1 с различными метаболическими нарушениями у пациентов с сахарным диабетом 1 типа (СД1).

Дизайн

Дизайн. Одномоментное кросс-секционное исследование.

Материалы и методы

Материалы и методы. Обследованы 147 неродственных пациентов с СД1. У них измеряли рост, массу тела, окружности талии и бедер, индекс массы тела. Лабораторные исследования включали определение уровней общего холестерина, холестерина липопротеинов высокой и низкой плотности, триглицеридов. Вариант нуклеотидной последовательности исследован при помощи полимеразной цепной реакции. С применением критерия χ2 оценено соответствие частоты генотипов равновесию Харди — Вайнберга. Анализ ассоциации генотипов с инсулинорезистентностью проводили с использованием онлайн-программы SNPStats. Анализ ассоциаций представлен в кодоминантной, доминантной, рецессивной, сверхдоминантной и аддитивной моделях, а также в ходе аллельного теста.

Результаты

Результаты. Распределение генотипов и аллелей варианта нуклеотидной последовательности rs3730089 гена PIK3R1 у всех пациентов соответствовало равновесию Харди — Вайнберга. Отмечена значимая ассоциация генотипов А/С и А/А в доминантных моделях с повышенными уровнями липопротеинов низкой плотности и холестерина. В сверхдоминантной модели определена ассоциация генотипа А/С с повышенным уровнем триглицеридов, а также с увеличенной окружностью талии и избыточной массой у пациентов с СД1 (отношение шансов — 10,5, 95% доверительный интервал: 3,94–27,99, р < 0,0001, рFDR = 0,0001 и отношение шансов — 5,70, 95% доверительный интервал: 2,28–14,26, р = 0,0001, рFDR = 0,0002 соответственно). Для всех вышеуказанных показателей аллель А был рисковым. Ассоциации генотипов и аллелей варианта нуклеотидной последовательности rs3730089 гена PIK3R1 с пониженным уровнем липопротеинов высокой плотности не найдены.

Заключение

Заключение. Нуклеотидная последовательность rs3730089 гена PIK3R1 связана с нарушениями липидного обмена у пациентов с СД1. Аллель А является рисковым. Данный вариант нуклеотидной последовательности может быть ассоциирован с инсулинорезистентностью у лиц с СД1.

Aim

Aim. To analyze the association of the rs3730089 nucleotide sequence variant of the PIK3R1 gene with various metabolic disorders in patients with type 1 diabetes mellitus (T1DM).

Design

Design. A one-stage cross-sectional study.

Materials and methods

Materials and methods. 147 unrelated patients with T1DM were examined. Their height, body weight, waist and hip circumferences, and body mass index were measured. Laboratory tests included the determination of total cholesterol, high- and low-density lipoprotein cholesterol, and triglycerides. The variant of the nucleotide sequence was investigated using a polymerase chain reaction. Using the χ2 criterion, the correspondence of the frequency of genotypes to the Hardy — Weinberg equilibrium was estimated. The association of genotypes with insulin resistance was analyzed using the online SNPStats program. Association analysis is presented in codominant, dominant, recessive, overdominant, and additive models, as well as during the allele test.

Results

Results. The distribution of genotypes and alleles of the rs3730089 nucleotide sequence variant of the PIK3R1 gene in all patients corresponded to the Hardy — Weinberg equilibrium. There was a significant association of A/C and A/A genotypes in dominant models with elevated levels of low-density lipoproteins and cholesterol. In the overdominant model, the association of the A/C genotype with elevated triglyceride levels, as well as with increased waist circumference and overweight in patients with Т1DM was determined (odds ratio — 10.5, 95% confidence interval: 3.94–27.99, p < 0.0001, рFDR = 0.0001 and odds ratio — 5.70, 95% confidence interval: 2.28–14.26, p = 0.0001, рFDR = 0.0002, respectively). For all of the above indicators, allele A was risky. Associations of genotypes and alleles of the rs3730089 nucleotide sequence variant of the PIK3R1 gene with a reduced level of high-density lipoproteins have not been found.

Conclusion

Conclusion. The nucleotide sequence rs3730089 of the PIK3R1 gene is associated with lipid metabolism disorders in patients with Т1DM.

Allele A is risky

Allele A is risky. This variant of the nucleotide sequence may be associated with insulin resistance in people with T1DM. 

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