Identification of Gender-Specific Genetic Variants in Patients With Bicuspid Aortic Valve

Autor: Nathalie Gaudreault, Maxime Lamontagne, Laura Sbarra, Natasha Dargis, Cyndi Henry, Yohan Bossé, Patrick Mathieu, Philippe Pibarot
Rok vydání: 2016
Předmět:
Male
0301 basic medicine
Aortic valve
medicine.medical_specialty
Pathology
Genotype
Population
Heart Valve Diseases
030204 cardiovascular system & hematology
Severity of Illness Index
03 medical and health sciences
symbols.namesake
Sex Factors
0302 clinical medicine
Bicuspid aortic valve
Bicuspid Aortic Valve Disease
Gene Frequency
Internal medicine
Genetic variation
Prevalence
medicine
Humans
Genetic Predisposition to Disease
Sex Distribution
education
Allele frequency
Aged
Sanger sequencing
Genetics
education.field_of_study
business.industry
Quebec
Genetic Variation
DNA
Ion semiconductor sequencing
Middle Aged
medicine.disease
3. Good health
030104 developmental biology
medicine.anatomical_structure
Echocardiography
Aortic Valve
symbols
Cardiology
Female
Cardiology and Cardiovascular Medicine
business
Zdroj: The American Journal of Cardiology. 117:420-426
ISSN: 0002-9149
Popis: Bicuspid aortic valve (BAV) is the most frequent congenital heart defect and has a male predominance of 3 to 1. A large proportion of patients develop valvular and aortic complications. Despite the high prevalence of BAV, its cause and genetic origins remain elusive. The goal of this study was to identify genetic variants associated with BAV. Nine genes previously associated with BAV (NOTCH1, AXIN1, EGFR, ENG, GATA5, NKX2-5, NOS3, PDIA2, and TGFBR2) were sequenced in 48 patients with BAV using the Ion Torrent Personal Genome Machine. Pathogenicity of genetic variants was evaluated with the Combined Annotation Dependent Depletion framework. A selection of 89 variants identified by sequencing or in previous BAV genetic studies was genotyped, and allele frequencies were compared in 323 patients with BAV confirmed at surgery and 584 controls. Analyses were also performed by gender. Nine novel and 19 potentially pathogenic variants were identified by next-generation sequencing and confirmed by Sanger sequencing, but they were not associated with BAV in the case-control population. A significant association was observed between an in silico-predicted benign EGFR intronic variant (rs17290301) and BAV. Analyses performed by gender revealed different variants associated with BAV in men (EGFR rs533525993 and TEX26 rs12857479) and women (NOTCH1 rs61751489, TGFBR2 rs1155705, and NKX2-5 rs2277923). In conclusion, these results constitute the first association between EGFR genetic variants and BAV in humans and support a possible role of gender-specific polymorphisms in the development of BAV.
Databáze: OpenAIRE
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