[TKIS-P] Takao International Session（II-TKIS-P）
e-Poster

[II-TKIS-P-7] Association of a Polygenic Risk Score with Pulmonary Valve Replacement in Repaired Tetralogy of Fallot

^○Takanori Suzuki^1,2, Sandar Min¹, Sean J Jurgens^3,4, Jade Bouwmeester¹, Robert Lesurf¹, Alex V. Postma^5,6, Gillian Blue⁷, David Winlaw⁸, Connie R Bezzina^3,9, Seema Mital^1,2,10 (1.Genetics and Genome Biology Program, Hospital for Sick Children, Toronto, Ontario, Canada, 2.Division of Cardiology, Department of Pediatrics, Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada, 3.Department of Experimental Cardiology, Amsterdam Cardiovascular Sciences, University of Amsterdam, Amsterdam UMC, Amsterdam, the Netherlands, 4.Cardiovascular Disease Initiative, Broad Institute of MIT and Harvard, Cambridge, MA, USA, 5.Department of Medical Biology, Amsterdam University Medical Center, Amsterdam, the Netherlands., 6.Department of Human Genetics, Amsterdam University Medical Center, Amsterdam, the Netherlands., 7.Heart Centre for Children, The Children's Hospital at Westmead, Sydney, NSW, Australia., 8.Ann and Robert H. Lurie Children's Hospital of Chicago, Chicago, Illinois, USA., 9.European Reference Network for Rare and Low Prevalence Complex Diseases of the Heart, 10.Ted Rogers Centre for Heart Research, Toronto, Ontario, Canada)

キーワード：

Tetralogy of Fallot、right ventricular remodeling、pulmonary valve replacement

Patients with repaired tetralogy of Fallot are at risk for progressive right ventricular dilation and dysfunction and often require pulmonary valve replacement. We assessed the association between a polygenic risk score and right ventricular dilation and pulmonary valve replacement in a multinational cohort of repaired tetralogy of Fallot. We analyzed common single nucleotide polymorphisms in 872 pediatric and adult patients from the international PROCEED study. A polygenic risk score for right ventricular end diastolic volume index was derived from a published genome wide association study in the UK Biobank and applied to the cohort using logistic regression with interaction analyses. Significant right ventricular dilation was observed in 44 percent of patients and 26 percent underwent pulmonary valve replacement. Moderate or severe pulmonary valve insufficiency transannular patch repair and male sex were associated with both outcomes. Higher polygenic risk score was associated with increased risk of right ventricular dilation and pulmonary valve replacement among patients without significant pulmonary valve insufficiency and this association was strongest in males although statistical significance was not reached. These findings suggest that genetic susceptibility contributes to adverse right ventricular remodeling independent of pulmonary valve insufficiency.