Genetic and phenotypic heterogeneity of type 2 diabetes across Russian ancestry groups.

IF 4.6 2区医学 Q2 ENDOCRINOLOGY & METABOLISM

Frontiers in Endocrinology Pub Date : 2025-09-10 eCollection Date: 2025-01-01 DOI:10.3389/fendo.2025.1672403

Ekaterina E Markelova, Irina V Kononenko, Anatoliy Zubritskiy, Elizaveta Podshivalova, Alina Matrosova, Evgeniya Plaksina, Saleem Mansour, Pavel Ahtyamov, Elena Shagimardanova, Gulnar R Vagapova, Nadezhda Maksimova, Liubov A Sydykova, Diana S Avzaletdinova, Tatyana V Morugova, Petimat M Dzhambetova, Marina V Shestakova, Natalia G Mokrysheva, Yulia A Medvedeva

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引用次数: 0

Abstract

Introduction: Type 2 diabetes mellitus (T2D) is a highly polygenic disease involving multiple biological pathways. Genetic ancestry may influence the predominant mechanisms driving T2D. Understanding how genetic background shapes T2D risk is crucial for developing personalized prevention and treatment strategies.

Methods: We analyzed ancestry-specific differences in T2D mechanisms and assessed the prevalence of T2D-associated genetic clusters, reflecting biological mechanisms underlying T2D onset and progression, in individuals from three Russian ancestry groups: Chechens, Tatars, and Yakuts. Previously developed polygenic scores were applied to evaluate cluster prevalence and clinical risk factors across ancestry groups.

Results: Cluster-specific polygenic scores varied significantly between populations. Yakuts exhibited higher scores for β-cell dysfunction, hyper-insulin secretion, and lipid metabolism alterations, whereas Chechens and Tatars had higher scores for obesity-related mechanisms.

Discussion/conclusions: The predominant mechanisms underlying T2D differ across populations. These ancestry-specific differences should be considered in public health recommendations and personalized medicine approaches.

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2型糖尿病在俄罗斯祖先群体中的遗传和表型异质性。

2型糖尿病（T2D）是一种涉及多种生物学途径的高多基因疾病。遗传祖先可能影响驱动T2D的主要机制。了解遗传背景如何影响T2D风险对于制定个性化的预防和治疗策略至关重要。方法：我们分析了T2D机制的谱系特异性差异，并评估了T2D相关遗传集群的患病率，反映了T2D发病和进展的生物学机制，这些个体来自三个俄罗斯血统群体：车臣人、鞑靼人和雅库特人。先前开发的多基因评分应用于评估跨祖先群体的群集患病率和临床危险因素。结果：群体特异性多基因评分差异显著。雅库特人在β细胞功能障碍、高胰岛素分泌和脂质代谢改变方面得分较高，而车臣人和鞑靼人在肥胖相关机制方面得分较高。讨论/结论：t2dm的主要机制因人群而异。在公共卫生建议和个性化医疗方法中应考虑这些特定血统的差异。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Frontiers in Endocrinology Medicine-Endocrinology, Diabetes and Metabolism

CiteScore

5.70

自引率

9.60%

发文量

3023

审稿时长

14 weeks

期刊介绍： Frontiers in Endocrinology is a field journal of the "Frontiers in" journal series. In today’s world, endocrinology is becoming increasingly important as it underlies many of the challenges societies face - from obesity and diabetes to reproduction, population control and aging. Endocrinology covers a broad field from basic molecular and cellular communication through to clinical care and some of the most crucial public health issues. The journal, thus, welcomes outstanding contributions in any domain of endocrinology. Frontiers in Endocrinology publishes articles on the most outstanding discoveries across a wide research spectrum of Endocrinology. The mission of Frontiers in Endocrinology is to bring all relevant Endocrinology areas together on a single platform.