The effection of gene variation in Familial
DOI:
https://doi.org/10.54097/pq337c45Keywords:
LDLR; PCSK9; APOB; familial hypercholesterolemia; founder effect.Abstract
Familial hypercholesterolemia (FH) is a genetic disorder characterized by significantly elevated levels of low-density lipoprotein cholesterol (LDL-C) in the blood, which increases the risk of atherosclerotic cardiovascular diseases (ASCVD). It is usually accompanied by tendinitis xanthomatosis and a family history of early-onset coronary heart disease. Mutations in LDLR, PCSK9, and APOB are the main pathogenic basis of FH. Although there have been many studies on FH in recent years, there has been no clear summary of the mutation types in the population, thus making it impossible to conduct targeted screening and medication for different FH patients. This review conducts an in-depth analysis of the distribution of mutations in the LDLR, PCSK9, and APOB genes, the impact of LDLR, PCSK9, and APOB mutations on FH, and summarizes the main mutation types of these three genes in different populations. This can further summarize the genetic basis of FH and provide a strong basis for the subsequent development of treatment strategies targeting specific mutation types.
Downloads
References
[1] Beheshti SO, Madsen CM, Varbo A, Nordestgaard BG. Worldwide prevalence of familial hypercholesterolemia: Meta-analyses of 11 million subjects. Journal of the American College of Cardiology, 2020, 75(20): 2553-66.
[2] Vos T, Lim SS, Abbafati C, Abbas KM, Abbasi-Kangevari M, Abd-Allah F, et al. Global burden of 369 diseases and injuries in 204 countries and territories, 1990–2019: A systematic analysis for the Global Burden of Disease Study 2019. The Lancet, 2020, 396(10258): 1204–22.
[3] Migliara G, Baccolini V, Rosso A, D’Andrea E, Massimi A, Villari P, et al. Familial hypercholesterolemia: A systematic review of guidelines on genetic testing and patient management. Frontiers in Public Health, 2017.
[4] Singapore Heart Foundation, https://www.myheart.org.sg/, Familial Hypercholesterolemia (FH) – For Clinicians.
[5] Abifadel M, Boileau C. Genetic and molecular architecture of familial hypercholesterolemia. J Intern Med, 2023, 293(2): 144-165.
[6] Tokgozoglu L, Kayikcioglu M. Familial Hypercholesterolemia: Global Burden and Approaches. Curr Cardiol Rep, 2021, 23(10): 151.
[7] Tichý L, Fajkusová L, Zapletalová P, Schwarzová L, Vrablík M, Freiberger T. Molecular genetic background of an autosomal dominant hypercholesterolemia in the Czech Republic. Physiol Res, 2017, 66(Suppl 1): S47-S54.
[8] R. Do, N.O. Stitziel, H.H. Won, et al. Exome sequencing identifies rare LDLR and APOA5 alleles conferring risk for myocardial infarction. Nature, 2014, advance online publication(7537): 102-6.
[9] Kindy, M. S. Review of p.(Val429Met), a Variant of LDLR That Is Associated with Familial Hypercholesterolemia. Cardiogenetics, 2024, 14.
[10] Huang CC, Niu DM, Charng MJ. Genetic Analysis in a Taiwanese Cohort of 750 Index Patients with Clinically Diagnosed Familial Hypercholesterolemia. J Atheroscler Thromb, 2022, 29(5): 639-653.
[11] Shin, D., Kim, S., Lee, H. et al. PCSK9 stimulates Syk, PKCδ, and NF-κB, leading to atherosclerosis progression independently of LDL receptor. Nat Commun 15, 2789 (2024).
[12] Mahdieh N, Heshmatzad K, Rabbani B. A systematic review of LDLR, PCSK9, and APOB variants in Asia. Atherosclerosis, 2020, 305: 50-57.
[13] Hori M, Ohta N, Takahashi A, Masuda H, Isoda R, Yamamoto S, Son C, Ogura M, Hosoda K, Miyamoto Y, Harada-Shiba M. Impact of LDLR and PCSK9 pathogenic variants in Japanese heterozygous familial hypercholesterolemia patients. Atherosclerosis, 2019, 289: 101-108.
[14] Humphries SE, Cranston T, Allen M, Middleton-Price H, Fernandez MC, Senior V, Hawe E, Iversen A, Wray R, Crook MA, Wierzbicki AS. Mutational analysis in UK patients with a clinical diagnosis of familial hypercholesterolaemia: relationship with plasma lipid traits, heart disease risk and utility in relative tracing. J Mol Med (Berl), 2006, 84(3): 203-14.
[15] Tybjaerg-Hansen,Anne,Watts,et al. Mutations causative of familial hypercholesterolaemia: screening of 98 098 individuals from the Copenhagen General Population Study estimated a prevalence of 1 in 217. European Heart Journal: The Journal of the European Society of Cardiology, 2016, 37(17): 1384-1394.
[16] Rogozik J , Rokicki J K , Grabowski M .Gene Mutation in Patients with Familial Hypercholesterolemia and Response to Alirocumab Treatment—A Single-Centre Analysis. 2024.
Downloads
Published
Issue
Section
License
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
