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 |
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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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