{"title":"Genetic and polygenic contributions to familial hypercholesterolemia in Thailand: Implications for diagnosis and lipid management.","authors":"Phongthana Pasookhush, Apinya Surawit, Sophida Suta, Sureeporn Pumeiam, Pichanun Mongkolsucharitkul, Bonggochpass Pinsawas, Suphawan Ophakas, Korapat Mayurasakorn","doi":"10.1016/j.jacl.2025.06.020","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Familial hypercholesterolemia (FH) is a major risk factor for cardiovascular diseases; however, the issue of underdiagnosis remains a global challenge. This study investigates the prevalence of FH-associated variants in Thailand and examines the clinical and lipid profile characteristics of variant carriers to improve diagnostic strategies.</p><p><strong>Methods: </strong>We analyzed the genetic data of 4879 participants across 2 cohorts, identifying variants in LDLR, APOB, and PCSK9. A 12-single-nucleotide polymorphism (12-SNP) polygenic risk score (PRS) for low-density lipoprotein cholesterol (LDL-C) was calculated. Longitudinal lipid profiles, including LDL-C, total cholesterol (TC), triglyceride, and high-density lipoprotein cholesterol (HDL-C) were assessed to evaluate the sustained impact of FH-associated variants.</p><p><strong>Results: </strong>FH-associated variants were identified in 0.59% of participants, with 68.96% carrying variants in LDLR and 31.04% in APOB. FH-associated variant carriers had significantly higher LDL-C (125.5 mg/dL vs 107.8 mg/dL, P =0.015) and TC levels (208.5 mg/dL vs 190.0 mg/dL, P = .004) than noncarriers, though overlap in lipid profiles was observed. PRS analysis revealed that FH-associated variants contributed more significantly to LDL-C levels than polygenic factors. Long-term follow-up showed persistent elevation of LDL-C and TC in FH-associated variant carriers.</p><p><strong>Conclusion: </strong>This study provides the first prevalence analysis of FH in Thailand, highlighting the limitations of lipid-based diagnostic criteria. Incorporating genetic screening and developing tailored diagnostic criteria are critical for addressing FH underdiagnosis and improving lipid management in Thailand.</p>","PeriodicalId":15392,"journal":{"name":"Journal of clinical lipidology","volume":" ","pages":""},"PeriodicalIF":4.6000,"publicationDate":"2025-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of clinical lipidology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1016/j.jacl.2025.06.020","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"PHARMACOLOGY & PHARMACY","Score":null,"Total":0}
引用次数: 0
Abstract
Background: Familial hypercholesterolemia (FH) is a major risk factor for cardiovascular diseases; however, the issue of underdiagnosis remains a global challenge. This study investigates the prevalence of FH-associated variants in Thailand and examines the clinical and lipid profile characteristics of variant carriers to improve diagnostic strategies.
Methods: We analyzed the genetic data of 4879 participants across 2 cohorts, identifying variants in LDLR, APOB, and PCSK9. A 12-single-nucleotide polymorphism (12-SNP) polygenic risk score (PRS) for low-density lipoprotein cholesterol (LDL-C) was calculated. Longitudinal lipid profiles, including LDL-C, total cholesterol (TC), triglyceride, and high-density lipoprotein cholesterol (HDL-C) were assessed to evaluate the sustained impact of FH-associated variants.
Results: FH-associated variants were identified in 0.59% of participants, with 68.96% carrying variants in LDLR and 31.04% in APOB. FH-associated variant carriers had significantly higher LDL-C (125.5 mg/dL vs 107.8 mg/dL, P =0.015) and TC levels (208.5 mg/dL vs 190.0 mg/dL, P = .004) than noncarriers, though overlap in lipid profiles was observed. PRS analysis revealed that FH-associated variants contributed more significantly to LDL-C levels than polygenic factors. Long-term follow-up showed persistent elevation of LDL-C and TC in FH-associated variant carriers.
Conclusion: This study provides the first prevalence analysis of FH in Thailand, highlighting the limitations of lipid-based diagnostic criteria. Incorporating genetic screening and developing tailored diagnostic criteria are critical for addressing FH underdiagnosis and improving lipid management in Thailand.
背景：家族性高胆固醇血症（FH）是心血管疾病的主要危险因素；然而，诊断不足的问题仍然是一个全球性的挑战。本研究调查了fh相关变异在泰国的流行情况，并检查了变异携带者的临床和血脂特征，以改进诊断策略。方法：我们分析了2个队列的4879名参与者的遗传数据，确定了LDLR、APOB和PCSK9的变异。计算低密度脂蛋白胆固醇（LDL-C）的12单核苷酸多态性（12-SNP）多基因风险评分（PRS）。纵向脂质谱，包括LDL-C、总胆固醇（TC）、甘油三酯和高密度脂蛋白胆固醇（HDL-C）进行评估，以评估fh相关变异的持续影响。结果：在0.59%的参与者中鉴定出fh相关变异，其中68.96%的参与者携带LDLR变异，31.04%的参与者携带APOB变异。fh相关变异携带者的LDL-C （125.5 mg/dL vs 107.8 mg/dL, P =0.015）和TC水平（208.5 mg/dL vs 190.0 mg/dL, P = 0.004）显著高于非携带者，尽管在脂质谱上观察到重叠。PRS分析显示，与多基因因素相比，fh相关变异对LDL-C水平的影响更为显著。长期随访显示，fh相关变异携带者LDL-C和TC持续升高。结论：本研究首次提供了泰国FH患病率分析，突出了基于脂质诊断标准的局限性。结合遗传筛查和制定有针对性的诊断标准对于解决FH漏诊问题和改善泰国的脂质管理至关重要。
期刊介绍：
Because the scope of clinical lipidology is broad, the topics addressed by the Journal are equally diverse. Typical articles explore lipidology as it is practiced in the treatment setting, recent developments in pharmacological research, reports of treatment and trials, case studies, the impact of lifestyle modification, and similar academic material of interest to the practitioner.
Sections of Journal of clinical lipidology will address pioneering studies and the clinicians who conduct them, case studies, ethical standards and conduct, professional guidance such as ATP and NCEP, editorial commentary, letters from readers, National Lipid Association (NLA) news and upcoming event information, as well as abstracts from the NLA annual scientific sessions and the scientific forums held by its chapters, when appropriate.
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