Influence of the IDOL Gene Variants on Low-Density Lipoprotein Cholesterol Levels in Turkish Patients with Familial Hypercholesterolemia.

IF 0.9 4区医学 Q4 GENETICS & HEREDITY

Molecular Syndromology Pub Date : 2025-04-01 Epub Date: 2024-08-30 DOI:10.1159/000540898

Fahrettin Duymus, Nadir Kocak, Ebru Marzioğlu Özdemir, Deniz Esin, Muslu Kazim Körez, Tülün Cora

{"title":"Influence of the IDOL Gene Variants on Low-Density Lipoprotein Cholesterol Levels in Turkish Patients with Familial Hypercholesterolemia.","authors":"Fahrettin Duymus, Nadir Kocak, Ebru Marzioğlu Özdemir, Deniz Esin, Muslu Kazim Körez, Tülün Cora","doi":"10.1159/000540898","DOIUrl":null,"url":null,"abstract":"Introduction: The inducible degrader of low-density lipoprotein (IDOL) receptor, an E3 ubiquitin ligase, was recently identified as a regulator of the LDL receptor (LDLR) pathway. Shortly, IDOL stimulates LDLR degradation through ubiquitination. However, the association of IDOL gene variants with plasma lipid levels is controversial. No previous study in the Turkish population has reported the relationship between variants of the IDOL gene and low-density lipoprotein cholesterol (LDL-C) levels. Our study aims to investigate the effects of genetic variants in the human IDOL gene, which may be a therapeutic target in human cholesterol metabolism, on LDL-C levels.Methods: We sequenced all coding, critical intronic, and untranslated regions of the IDOL gene in 125 controls (77 women, 48 men) and 125 patients (64 women, 61 men) with definite or probable familial hypercholesterolemia (FH) according to the criteria of the Dutch Lipid Clinic Network, in whom no pathogenic/likely pathogenic LDLR variants are present.Results: We identified 12 different IDOL gene variants, including the p.(N342S) and p.(G51S), whose association with LDL-C levels has been investigated, and classified them into common and rare variants. A rare variant p.(G51S) was only detected in patients the patient group. We compared the minor allele frequency (MAF) distribution of common variants between patient and control groups and examined the association of their genotypic distribution with plasma LDL-C levels using genetic models (dominant, recessive, overdominant, codominant). There was no statistically significant difference in the parameters of the patient and control groups (p > 0.05).Conclusion: Our findings suggest that the common IDOL variants we identified do not associate with the LDL-C level in the Turkish population. Rare variants that were not found to be statistically significant in our study, should be emphasized, and supported with further research.","PeriodicalId":48566,"journal":{"name":"Molecular Syndromology","volume":"16 2","pages":"128-137"},"PeriodicalIF":0.9000,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11961089/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Molecular Syndromology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1159/000540898","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/8/30 0:00:00","PubModel":"Epub","JCR":"Q4","JCRName":"GENETICS & HEREDITY","Score":null,"Total":0}

引用次数: 0

Abstract

Introduction: The inducible degrader of low-density lipoprotein (IDOL) receptor, an E3 ubiquitin ligase, was recently identified as a regulator of the LDL receptor (LDLR) pathway. Shortly, IDOL stimulates LDLR degradation through ubiquitination. However, the association of IDOL gene variants with plasma lipid levels is controversial. No previous study in the Turkish population has reported the relationship between variants of the IDOL gene and low-density lipoprotein cholesterol (LDL-C) levels. Our study aims to investigate the effects of genetic variants in the human IDOL gene, which may be a therapeutic target in human cholesterol metabolism, on LDL-C levels.

Methods: We sequenced all coding, critical intronic, and untranslated regions of the IDOL gene in 125 controls (77 women, 48 men) and 125 patients (64 women, 61 men) with definite or probable familial hypercholesterolemia (FH) according to the criteria of the Dutch Lipid Clinic Network, in whom no pathogenic/likely pathogenic LDLR variants are present.

Results: We identified 12 different IDOL gene variants, including the p.(N342S) and p.(G51S), whose association with LDL-C levels has been investigated, and classified them into common and rare variants. A rare variant p.(G51S) was only detected in patients the patient group. We compared the minor allele frequency (MAF) distribution of common variants between patient and control groups and examined the association of their genotypic distribution with plasma LDL-C levels using genetic models (dominant, recessive, overdominant, codominant). There was no statistically significant difference in the parameters of the patient and control groups (p > 0.05).

Conclusion: Our findings suggest that the common IDOL variants we identified do not associate with the LDL-C level in the Turkish population. Rare variants that were not found to be statistically significant in our study, should be emphasized, and supported with further research.

查看原文本刊更多论文

IDOL基因变异对土耳其家族性高胆固醇血症患者低密度脂蛋白胆固醇水平的影响

导言：低密度脂蛋白受体诱导降解器（IDOL）是一种 E3 泛素连接酶，最近被确认为低密度脂蛋白受体（LDLR）通路的调节因子。不久，IDOL 通过泛素化作用刺激 LDLR 降解。然而，IDOL 基因变异与血浆血脂水平的关系还存在争议。此前没有针对土耳其人群的研究报告了 IDOL 基因变异与低密度脂蛋白胆固醇（LDL-C）水平之间的关系。我们的研究旨在调查人类 IDOL 基因变异对 LDL-C 水平的影响，该基因可能是人类胆固醇代谢的治疗靶点：我们对 125 名对照组（77 名女性，48 名男性）和 125 名根据荷兰血脂诊疗网络标准确诊或可能患有家族性高胆固醇血症（FH）的患者（64 名女性，61 名男性）的 IDOL 基因的所有编码区、关键内含子区和非翻译区进行了测序，这些患者体内不存在致病性/可能致病性 LDLR 变异：我们发现了12种不同的IDOL基因变异，包括p.(N342S)和p.(G51S)，这些变异与低密度脂蛋白胆固醇水平的关系已得到研究，并将它们分为常见变异和罕见变异。罕见变异 p.(G51S) 仅在患者组中检测到。我们比较了患者组和对照组之间常见变异的小等位基因频率（MAF）分布，并使用遗传模型（显性、隐性、过显性、共显性）研究了其基因型分布与血浆 LDL-C 水平的关联。患者组和对照组的参数差异无统计学意义（P > 0.05）：我们的研究结果表明，我们发现的常见 IDOL 变异与土耳其人群的低密度脂蛋白胆固醇水平无关。在我们的研究中未发现有统计学意义的罕见变异，应予以重视，并通过进一步的研究予以支持。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Molecular Syndromology Biochemistry, Genetics and Molecular Biology-Genetics

CiteScore

1.70

自引率

9.10%

发文量

期刊介绍： ''Molecular Syndromology'' publishes high-quality research articles, short reports and reviews on common and rare genetic syndromes, aiming to increase clinical understanding through molecular insights. Topics of particular interest are the molecular basis of genetic syndromes, genotype-phenotype correlation, natural history, strategies in disease management and novel therapeutic approaches based on molecular findings. Research on model systems is also welcome, especially when it is obviously relevant to human genetics. With high-quality reviews on current topics the journal aims to facilitate translation of research findings to a clinical setting while also stimulating further research on clinically relevant questions. The journal targets not only medical geneticists and basic biomedical researchers, but also clinicians dealing with genetic syndromes. With four Associate Editors from three continents and a broad international Editorial Board the journal welcomes submissions covering the latest research from around the world.