ADAM9 Genetic Variants and Their Role in Modulating Enzyme Activity in Diabetes and Metabolic Traits.

IF 3.4 3区医学 Q2 ENDOCRINOLOGY & METABOLISM

Journal of Diabetes Research Pub Date : 2025-04-28 eCollection Date: 2025-01-01 DOI:10.1155/jdr/5519447

Hana Drobiova, Fahd Al-Mulla, Rabeah Al-Temaimi

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Abstract

A disintegrin and metalloproteinase Domain 9 (ADAM9) is a zinc-dependent proteinase involved in various biological processes. However, its role in the pathophysiology of metabolic syndrome remains unclear, and studies exploring the association between ADAM9 polymorphisms and metabolic traits are limited. In this study, we investigated the potential link between ADAM9 variants and metabolic syndrome traits in a cohort of adult participants from Kuwait. Using a genome-wide association study (GWAS), followed by a replication study, we identified two ADAM9 variants-ADAM9-E76K (rs61753672) and ADAM9-P750L (rs144750648)-that were associated with various metabolic traits. The replication phase confirmed the association of ADAM9-P750L with HbA1c levels and revealed new associations with systolic blood pressure, waist-to-hip ratio, fasting blood glucose, triglycerides, and cholesterol. Functional analysis showed that both variants exhibited reduced proteolytic activity, potentially contributing to the pathogenesis of Type 2 diabetes. These findings suggest that ADAM9 variants may play a significant role in metabolic health and diabetes risk.

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ADAM9基因变异及其在糖尿病和代谢性状中调节酶活性的作用

崩解素和金属蛋白酶结构域9 （ADAM9）是一种锌依赖性蛋白酶，参与多种生物过程。然而，其在代谢综合征病理生理中的作用尚不清楚，探索ADAM9多态性与代谢性状之间关系的研究也很有限。在这项研究中，我们调查了来自科威特的一组成年参与者的ADAM9变异与代谢综合征特征之间的潜在联系。通过全基因组关联研究（GWAS）和随后的复制研究，我们确定了两个ADAM9变异——ADAM9- e76k （rs61753672）和ADAM9- p750l （rs144750648）——它们与各种代谢性状相关。复制阶段证实了ADAM9-P750L与HbA1c水平的关联，并揭示了与收缩压、腰臀比、空腹血糖、甘油三酯和胆固醇的新关联。功能分析显示，这两种变体都表现出蛋白水解活性降低，可能与2型糖尿病的发病机制有关。这些发现表明，ADAM9变异可能在代谢健康和糖尿病风险中发挥重要作用。

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

Journal of Diabetes Research ENDOCRINOLOGY & METABOLISM-MEDICINE, RESEARCH & EXPERIMENTAL

CiteScore

8.40

自引率

2.30%

发文量

152

审稿时长

14 weeks

期刊介绍： Journal of Diabetes Research is a peer-reviewed, Open Access journal that publishes research articles, review articles, and clinical studies related to type 1 and type 2 diabetes. The journal welcomes submissions focusing on the epidemiology, etiology, pathogenesis, management, and prevention of diabetes, as well as associated complications, such as diabetic retinopathy, neuropathy and nephropathy.