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Clinical Expression of Familial Hypercholesterolemia in Patients from France and French Canada Carrying Identical by Descent Pathogenic LDLR Gene Variants: a Proof-of-Concept Study
Version 1
: Received: 4 September 2024 / Approved: 4 September 2024 / Online: 6 September 2024 (10:26:59 CEST)
How to cite:
Larouche, M.; Bluteau, O.; Carrié, A.; Lauzière, A.; Khoury, E.; Brisson, D.; Gaudet, D.; Gallo, A. Clinical Expression of Familial Hypercholesterolemia in Patients from France and French Canada Carrying Identical by Descent Pathogenic LDLR Gene Variants: a Proof-of-Concept Study. Preprints2024, 2024090522. https://doi.org/10.20944/preprints202409.0522.v1
Larouche, M.; Bluteau, O.; Carrié, A.; Lauzière, A.; Khoury, E.; Brisson, D.; Gaudet, D.; Gallo, A. Clinical Expression of Familial Hypercholesterolemia in Patients from France and French Canada Carrying Identical by Descent Pathogenic LDLR Gene Variants: a Proof-of-Concept Study. Preprints 2024, 2024090522. https://doi.org/10.20944/preprints202409.0522.v1
Larouche, M.; Bluteau, O.; Carrié, A.; Lauzière, A.; Khoury, E.; Brisson, D.; Gaudet, D.; Gallo, A. Clinical Expression of Familial Hypercholesterolemia in Patients from France and French Canada Carrying Identical by Descent Pathogenic LDLR Gene Variants: a Proof-of-Concept Study. Preprints2024, 2024090522. https://doi.org/10.20944/preprints202409.0522.v1
APA Style
Larouche, M., Bluteau, O., Carrié, A., Lauzière, A., Khoury, E., Brisson, D., Gaudet, D., & Gallo, A. (2024). Clinical Expression of Familial Hypercholesterolemia in Patients from France and French Canada Carrying Identical by Descent Pathogenic LDLR Gene Variants: a Proof-of-Concept Study. Preprints. https://doi.org/10.20944/preprints202409.0522.v1
Chicago/Turabian Style
Larouche, M., Daniel Gaudet and Antonio Gallo. 2024 "Clinical Expression of Familial Hypercholesterolemia in Patients from France and French Canada Carrying Identical by Descent Pathogenic LDLR Gene Variants: a Proof-of-Concept Study" Preprints. https://doi.org/10.20944/preprints202409.0522.v1
Abstract
Background: Studying patients carrying identical by descent (IBD) pathogenic gene variants allows to control for the disease-causing genetic background and to more accurately document the impact of modifiers. Familial hypercholesterolemia (FH) is characterized by elevated LDL-c levels, premature atherosclerosis and is often caused by defects in the LDLR gene. There is a high prevalence of FH in French Canada carry IBD FH-causing due to a founder effect from France in the 17th Century. Several FH patients currently living in French Canada (founder population) and in France (colonizing population) carry IBD FH-causing variants. The expression of FH is affected by environmental and genetic modifiers and patients with IBD variants may present different characteristics. Methods: In this study, we compared FH clinical expression patients carrying IBD LDLR pathogenic variants living in France or Canada. Four IBD variants, namely c.259T>G p.(Trp87Gly); c.2000G>A p.(Cys667Tyr); c.682G>A p.(Glu228Lys); and c.1048C>T p.(Arg350*) were selected. Untreated plasma lipid profiles, APOE genotype, cardiovascular risk factors and occurrence of symptomatic ASCVD were compared in 105 adult carriers (30 from France and 75 from French Canada). Results: All parameters were similar between the two populations, except for untreated total cholesterol (10.14 ± 1.89 mmol/L vs 8.65 ± 1.84 mmol/L, p=0.0006) and LDL-c concentrations (7.94 ± 1.86 mmol/L vs 6.93 ± 1.78 mmol/L, p=0.016) that were significantly higher in FH patients living in France, a trend that was observed in all studied LDLR variants. Conclusion: This study illustrates that FH patients sharing IBD pathogenic LDLR variants that have evolved in different geographic, cultural and socio-economic environments for hundreds of years, differ in term of cholesterol levels highlighting the importance of better understanding the interplay between genetic and environmental modulators of FH expression.
Keywords
Familial hypercholesterolemia; Founder effect; Identical by descent variant
Subject
Medicine and Pharmacology, Other
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
