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Rosa, Mickael

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  • PublicationAccès libre
    A transcriptome-wide association study identifies PALMD as a susceptibility gene for calcific aortic valve stenosis
    (Nature Publishing Group, 2018-03-07) Gaudreault, Nathalie; Thériault, Sébastien; Rosa, Mickael; Boulanger, Marie-Chloé; Capoulade, Romain; Messika-Zeitoun, David; Bossé, Yohan; Lamontagne, Maxime; Pibarot, Philippe; Clavel, Marie-Annick; Dagenais, François; Mathieu, Patrick
    Calcific aortic valve stenosis (CAVS) is a common and life-threatening heart disease and the current treatment options cannot stop or delay its progression. A GWAS on 1009 cases and 1017 ethnically matched controls was combined with a large-scale eQTL mapping study of human aortic valve tissues (n = 233) to identify susceptibility genes for CAVS. Replication was performed in the UK Biobank, including 1391 cases and 352,195 controls. A tran- scriptome-wide association study (TWAS) reveals PALMD (palmdelphin) as significantly associated with CAVS. The CAVS risk alleles and increasing disease severity are both associated with decreased mRNA expression levels of PALMD in valve tissues. The top variant identified shows a similar effect and strong association with CAVS (P = 1.53 × 10−10) in UK Biobank. The identification of PALMD as a susceptibility gene for CAVS provides insights into the genetic nature of this disease, opens avenues to investigate its etiology and to develop much-needed therapeutic options.
  • PublicationAccès libre
    Age, sex and valve phenotype differences in fibro-calcific remodeling of calcified aortic valve
    (John Wiley & Sons, 2020-05-08) Voisine, Martine; Rosa, Mickael; Hervault, Maxime; Shen, Mylène; Filion, Benoît; Boilard, Anne-Julie; Côté, Nancy; Bossé, Yohan; Clavel, Marie-Annick; Mathieu, Patrick
    Background: In calcific aortic valve disease (CAVD) on tricuspid aortic valves (TAV), men have higher aortic valve calcification (AVC) and less fibrosis than women. However, little is known in bicuspid aortic valves (BAV). We thus aimed to investigate the impact of age, sex, and valve phenotype (TAV vs BAV) on fibro-calcific remodeling in CAVD. Methods and Results: We included 2 cohorts: 411 patients who underwent multidetector-computed-tomography (MDCT-cohort; 37% women) for AVC density assessment and 138 explanted aortic valves (histological-cohort; 50% women). The cohorts were divided in younger (YBAV: ˂60 years old) or older patients with BAV (OBAV: ≥60 years old), and TAV patients. In each group, women and men were matched. Women presented less AVC density than men in each groups of the MDCT-cohort (all p≤0.01). Moreover, in women, YBAV had the lowest AVC density (both p=0.02). In multivariate analysis, AVC density correlated with age (β-estimate±Standard-error: 6.5±1.8; p=0.0004), male sex (109.2±18.4; p<0.0001), and there was a trend with TAV (41.5±23.0; p=0.07). Women presented a higher collagen content than men (77.8±10.8 vs 69.9±12.9%; p<0.001) in the entire cohort. In women, YBAV had denser connective tissue than TAV and OBAV (both p≤0.05) while no difference was observed between men. Conclusions: In CAVD, women presented less calcification and more fibrotic remodeling than men, regardless of the phenotype of the valve or age of the patient. Moreover, younger women with bicuspid valves had less valve calcification. Thus, mineralization/fibrosis of the aortic valve is likely to have sex/age-specific-mechanisms and be influenced by the valve morphology.