Review of p.(Val429Met), a Variant of <i>LDLR</i> That Is Associated with Familial Hypercholesterolemia
Patients affected by familial hypercholesterolemia possess elevated low-density lipoprotein cholesterol and therefore have greater risk for cardiovascular disease. About 90% of familial hypercholesterolemia cases are associated with aberrant <i>LDLR</i>. Over 3500 <i>LDLR</i>...
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| Main Authors: | , |
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| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2024-09-01
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| Series: | Cardiogenetics |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2035-8148/14/4/13 |
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| Summary: | Patients affected by familial hypercholesterolemia possess elevated low-density lipoprotein cholesterol and therefore have greater risk for cardiovascular disease. About 90% of familial hypercholesterolemia cases are associated with aberrant <i>LDLR</i>. Over 3500 <i>LDLR</i> variants have been identified, 15% of which are considered “pathogenic.” Given the genetic diversity of <i>LDLR</i> variants, specific variants rarely receive attention. However, investigators have proposed the critical evaluation of individual variants as a method to clarify knowledge and to resolve discrepancies in the literature. This article reviews p.(Val429Met) (rs28942078) in the areas of pathology, epidemiology, lipid-lowering therapy, and genetic testing. The p.(Val429Met) variant is associated with a missense point substitution in exon 9 of chromosome 19. Biochemical studies have found severely reduced low-density lipoprotein receptor protein in autologous and heterologous expression systems. Additionally, there are inconsistencies regarding the functional classification of p.(Val429Met). Considered to be of European origin, p.(Val429Met) is found in extant populations due to founder effects. Evidence from clinical trials have also demonstrated variable responses to newer lipid-lowering therapies in patients with a p.(Val429Met) variant. Proper clinical detection and adequate genetic testing have been shown to greatly improve outcomes. Future research may be aimed at resolving discrepancies to better comprehend the implications of familial hypercholesterolemia. |
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| ISSN: | 2035-8253 2035-8148 |