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一个包含 8 个单核苷酸多态性的 LDL 胆固醇多基因评分:与心血管风险特征、家族性高胆固醇血症表型和罗马尼亚中部的早发性冠心病的相关性。

An 8-SNP LDL Cholesterol Polygenic Score: Associations with Cardiovascular Risk Traits, Familial Hypercholesterolemia Phenotype, and Premature Coronary Heart Disease in Central Romania.

机构信息

Department of Laboratory Medicine, Faculty of Medicine, George Emil Palade University of Medicine, Pharmacy, Science, and Technology of Targu Mures, 540142 Targu Mures, Romania.

Department of Economic Science, Faculty of Economics and Law, George Emil Palade University of Medicine, Pharmacy, Science, and Technology of Targu Mures, 540566 Targu Mures, Romania.

出版信息

Int J Mol Sci. 2024 Sep 18;25(18):10038. doi: 10.3390/ijms251810038.


DOI:10.3390/ijms251810038
PMID:39337524
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11432653/
Abstract

Familial hypercholesterolemia (FH) is the most significant inherited risk factor for coronary heart disease (CHD). Current guidelines focus on monogenic FH, but the polygenic form is more common and less understood. This study aimed to assess the clinical utility of an 8-SNP LDLC polygenic score in a central Romanian cohort. The cohort included 97 healthy controls and 125 patients with premature (P)CHD. The weighted LDLC polygenic risk score (wPRS) was analyzed for associations with relevant phenotypic traits, PCHD risk, and clinical FH diagnosis. The wPRS positively correlated with LDLC and DLCN scores, and LDLC concentrations could be predicted by wPRS. A trend of increasing LDLC and DLCN scores with wPRS deciles was observed. A +1 SD increase in wPRS was associated with a 36% higher likelihood of having LDLC > 190 mg/dL and increases in LDLC (+0.20 SD), DLCN score (+0.16 SD), and BMI (+0.15 SD), as well as a decrease in HDLC (-0.14 SD). Although wPRS did not predict PCHD across the entire spectrum of values, individuals above the 90th percentile were three times more likely to have PCHD compared to those within the 10th or 20th percentiles. Additionally, wPRS > 45th percentile identified "definite" clinical FH (DLCN score > 8) with 100% sensitivity and 45% specificity. The LDLC polygenic score correlates with key phenotypic traits, and individuals with high scores are more likely to have PCHD. Implementing this genetic tool may enhance risk prediction and patient stratification. These findings, the first of their kind in Romania, are consistent with the existing literature.

摘要

家族性高胆固醇血症(FH)是冠心病(CHD)最重要的遗传危险因素。目前的指南侧重于单基因 FH,但多基因形式更为常见,也不太了解。本研究旨在评估 8 个 SNP LDLC 多基因评分在罗马尼亚中部队列中的临床应用价值。该队列包括 97 名健康对照者和 125 名早发性(P)CHD 患者。分析加权 LDLC 多基因风险评分(wPRS)与相关表型特征、PCHD 风险和临床 FH 诊断的相关性。wPRS 与 LDLC 和 DLCN 评分呈正相关,并且可以通过 wPRS 预测 LDLC 浓度。观察到 LDLC 和 DLCN 评分随 wPRS 十分位数的增加呈增加趋势。wPRS 增加 1 SD 与 LDLC > 190 mg/dL 的可能性增加 36%相关,并且与 LDLC(+0.20 SD)、DLCN 评分(+0.16 SD)和 BMI(+0.15 SD)增加以及 HDLC(-0.14 SD)减少相关。尽管 wPRS 不能预测整个值范围内的 PCHD,但与第 10 或 20 百分位的个体相比,位于第 90 百分位以上的个体发生 PCHD 的可能性高 3 倍。此外,wPRS > 45 百分位可以识别出具有 100%敏感性和 45%特异性的“明确”临床 FH(DLCN 评分> 8)。LDLC 多基因评分与关键表型特征相关,高分者更有可能发生 PCHD。实施这种遗传工具可能会增强风险预测和患者分层。这些发现是罗马尼亚首例此类发现,与现有文献一致。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fb96/11432653/ae27f2e7275f/ijms-25-10038-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fb96/11432653/ace0de581eb3/ijms-25-10038-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fb96/11432653/b776663158e1/ijms-25-10038-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fb96/11432653/506ff24fe014/ijms-25-10038-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fb96/11432653/51b8df024609/ijms-25-10038-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fb96/11432653/779891769247/ijms-25-10038-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fb96/11432653/ae27f2e7275f/ijms-25-10038-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fb96/11432653/ace0de581eb3/ijms-25-10038-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fb96/11432653/b776663158e1/ijms-25-10038-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fb96/11432653/506ff24fe014/ijms-25-10038-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fb96/11432653/51b8df024609/ijms-25-10038-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fb96/11432653/779891769247/ijms-25-10038-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fb96/11432653/ae27f2e7275f/ijms-25-10038-g006.jpg

相似文献

[1]
An 8-SNP LDL Cholesterol Polygenic Score: Associations with Cardiovascular Risk Traits, Familial Hypercholesterolemia Phenotype, and Premature Coronary Heart Disease in Central Romania.

Int J Mol Sci. 2024-9-18

[2]
Greater preclinical atherosclerosis in treated monogenic familial hypercholesterolemia vs. polygenic hypercholesterolemia.

Atherosclerosis. 2017-5-13

[3]
Preliminary data of familial hypercholesterolemia (FH) patients in Romania.

Atherosclerosis. 2018-10

[4]
Polygenic Contribution to Low-Density Lipoprotein Cholesterol Levels and Cardiovascular Risk in Monogenic Familial Hypercholesterolemia.

Circ Genom Precis Med. 2020-10

[5]
Lipid phenotype and heritage pattern in families with genetic hypercholesterolemia not related to LDLR, APOB, PCSK9, or APOE.

J Clin Lipidol. 2016

[6]
Refinement of variant selection for the LDL cholesterol genetic risk score in the diagnosis of the polygenic form of clinical familial hypercholesterolemia and replication in samples from 6 countries.

Clin Chem. 2015-1

[7]
Clinical utility of the polygenic LDL-C SNP score in familial hypercholesterolemia.

Atherosclerosis. 2018-10

[8]
Impact of 12-SNP and 6-SNP Polygenic Scores on Predisposition to High LDL-Cholesterol Levels in Patients with Familial Hypercholesterolemia.

Genes (Basel). 2024-4-6

[9]
Influence of Polygenic Background on the Clinical Presentation of Familial Hypercholesterolemia.

Arterioscler Thromb Vasc Biol. 2024-7

[10]
Evaluation of polygenic cause in Korean patients with familial hypercholesterolemia - A study supported by Korean Society of Lipidology and Atherosclerosis.

Atherosclerosis. 2015-6-30

本文引用的文献

[1]
Impact of 12-SNP and 6-SNP Polygenic Scores on Predisposition to High LDL-Cholesterol Levels in Patients with Familial Hypercholesterolemia.

Genes (Basel). 2024-4-6

[2]
Polygenic risk score for hypercholesterolemia in a Brazilian familial hypercholesterolemia cohort.

Atheroscler Plus. 2022-6-28

[3]
The clinical utility of polygenic risk scores for combined hyperlipidemia.

Curr Opin Lipidol. 2023-4-1

[4]
A new 165-SNP low-density lipoprotein cholesterol polygenic risk score based on next generation sequencing outperforms previously published scores in routine diagnostics of familial hypercholesterolemia.

Transl Res. 2023-5

[5]
Genetic Factors for Coronary Heart Disease and Their Mechanisms: A Meta-Analysis and Comprehensive Review of Common Variants from Genome-Wide Association Studies.

Diagnostics (Basel). 2022-10-21

[6]
LDL-C Concentrations and the 12-SNP LDL-C Score for Polygenic Hypercholesterolaemia in Self-Reported South Asian, Black and Caribbean Participants of the UK Biobank.

Front Genet. 2022-3-31

[7]
Twelve Variants Polygenic Score for Low-Density Lipoprotein Cholesterol Distribution in a Large Cohort of Patients With Clinically Diagnosed Familial Hypercholesterolemia With or Without Causative Mutations.

J Am Heart Assoc. 2022-4-5

[8]
Assessment of practical applicability and clinical relevance of a commonly used LDL-C polygenic score in patients with severe hypercholesterolemia.

Atherosclerosis. 2022-1

[9]
Next-generation sequencing to confirm clinical familial hypercholesterolemia.

Eur J Prev Cardiol. 2021-7-23

[10]
Polygenic risk scores for low-density lipoprotein cholesterol and familial hypercholesterolemia.

J Hum Genet. 2021-11

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