Hilary S. Gammill|Rakesh Chettier|Alina Brewer|James M. Roberts|Raj Shree|Eleni Tsigas|Kenneth Ward
Cardiomyopathy and Preeclampsia
Cape Town HVTN Immunology Laboratory / Hutchinson Centre Research Institute of South Africa|Fred Hutch Cancer Center|Cancer Research Center|University of Washington|Deseret Laboratories (United States)|Deseret Laboratories (United States)|Preeclampsia Foundation|Magee-Womens Research Institute|University of Pittsburgh|University of Washington|Preeclampsia Foundation|Deseret Laboratories (United States)
background preeclampsia associated diastolic dysfunction peripartum cardiomyopathy preexisting subsequent maternal cardiovascular disease gene mutations causing idiopathic cardiomyopathy recently implicated peripartum cardiomyopathy sought determine whether cardiomyopathy gene mutations also contributory factor preeclampsia methods subjects participants preeclampsia registry biobank providing informed consent subjects history preeclampsia completed detailed questionnaire provided medical records diagnostic confirmation saliva samples collected dna isolation whole exome sequencing performed detect rare variants minor allele frequency lt01 43 genes associated cardiomyopathy missense variants deemed damaging missense classified 7 standard function prediction algorithms variants defined lossoffunction caused stopgain splicing frameshift insertion deletion results compared data 2 control groups unrelated women gynecologic disorder sequenced using methods instruments n530 well published variant data 33 000 subjects exome aggregation consortium preeclampsia excluded control groups results 181 subjects confirmed preeclampsia 96 white seventytwo percent 1 preterm preeclampsia delivery lt37 weeks among preeclampsia subjects whole exome sequencing demonstrated 10 rare lossoffunction variants 228 rare damaging missense variants 43 cardiomyopathy genes considered prevalence lossoffunction variants significantly higher preeclampsia subjects 55 compared local control 25 population p 0014 sixtyeight percent women preeclampsia carried 1 lossoffunction damaging missense variant mean 194 mutations seen peripartum cardiomyopathy mutations 55 found ttn gene seventythree percent preeclampsia subjects ttn mutations preeclampsia cohort versus 48 local controls p 136e11 discussion women develop preeclampsia likely carry proteinaltering mutations genes associated cardiomyopathy particularly ttn mutations promoting cardiomyopathy prevalent preeclampsia idiopathic cardiomyopathy peripartum cardiomyopathy important risk factors widening spectrum cardiovascular disorders detecting variants allow specific diagnosis classification counseling management women risk