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Influence of Genetic Variation in PDE3A on Endothelial Function and Stroke

Hypertension (Dallas, Tex. 1979), 2020-02, Vol.75 (2), p.365-371 [Peer Reviewed Journal]

2020 American Heart Association, Inc ;2019 The Authors. 2019 ;ISSN: 0194-911X ;EISSN: 1524-4563 ;DOI: 10.1161/HYPERTENSIONAHA.119.13513 ;PMID: 31865795

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Title:
Influence of Genetic Variation in PDE3A on Endothelial Function and Stroke
Author: Traylor, Matthew ; Amin Al Olama, Ali ; Lyytikäinen, Leo-Pekka ; Marini, Sandro ; Chung, Jaeyoon ; Malik, Rainer ; Dichgans, Martin ; Kähönen, Mika ; Lehtimäki, Terho ; Anderson, Christopher D ; Raitakari, Olli T ; Markus, Hugh S
Subjects: Adolescent ; Adult ; Brain Ischemia - etiology ; Brain Ischemia - genetics ; Child ; Cyclic Nucleotide Phosphodiesterases, Type 3 - genetics ; Cyclic Nucleotide Phosphodiesterases, Type 3 - metabolism ; Endothelium, Vascular - physiopathology ; Female ; Follow-Up Studies ; Genetic Predisposition to Disease ; Genetic Variation ; Humans ; Hypertension - complications ; Hypertension - genetics ; Hypertension - metabolism ; Male ; Middle Aged ; Original ; Polymorphism, Single Nucleotide ; Pregnancy ; Pregnancy Complications, Cardiovascular - genetics ; Pregnancy Complications, Cardiovascular - metabolism ; Pregnancy Complications, Cardiovascular - physiopathology ; Retrospective Studies ; Risk Factors ; Vasodilation - physiology ; Young Adult
Is Part Of: Hypertension (Dallas, Tex. 1979), 2020-02, Vol.75 (2), p.365-371
Description: We aimed to characterize the genetics of endothelial function and how this influences risk for cardiovascular diseases such as ischemic stroke. We integrated genetic data from a study of ultrasound flow-mediated dilatation of brachial artery in adolescents from ALSPAC (Avon Longitudinal Study of Parents and Children; n=5214) with a study of ischemic stroke (MEGASTROKEn=60 341 cases and 452 969 controls) to identify variants that confer risk of ischemic stroke through altered endothelial function. We identified a variant in PDE3A (Phosphodiesterase 3A), encoding phosphodiesterase 3A, which was associated with flow-mediated dilatation in adolescents (9–12 years of age; β[SE], 0.38 [0.070]; P=3.8×10) and confers risk of ischemic stroke (odds ratio, 1.04 [95% CI, 1.02–1.06]; P=5.2×10). Bayesian colocalization analyses showed the same underlying variation is likely to lead to both associations (posterior probability, 97%). The same variant was associated with flow-mediated dilatation in a second study in young adults (age, 24–27 years; β[SE], 0.47 [0.23]; P=0.047) but not in older adults (β[SE], −0.012 [0.13]; P=0.89). We conclude that a genetic variant in PDE3A influences endothelial function in early life and leads to increased risk of ischemic stroke. Subtle, measurable changes to the vasculature that are influenced by genetics also influence risk of ischemic stroke.
Publisher: United States: American Heart Association, Inc
Language: English
Identifier: ISSN: 0194-911X
EISSN: 1524-4563
DOI: 10.1161/HYPERTENSIONAHA.119.13513
PMID: 31865795
Source: Geneva Foundation Free Medical Journals at publisher websites
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Influence of Genetic Variation in PDE3A on Endothelial Function and Stroke

2020 American Heart Association, Inc ;2019 The Authors. 2019 ;ISSN: 0194-911X ;EISSN: 1524-4563 ;DOI: 10.1161/HYPERTENSIONAHA.119.13513 ;PMID: 31865795

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