Shared Genes in Preeclampsia and Cardiomyopathy

Study Questions:

Do women with preeclampsia have a higher prevalence of gene mutations associated with cardiomyopathy?


Subjects from The Preeclampsia Registry and Biobank submitted saliva samples for DNA isolation. Whole exome sequencing (WES) was performed to detect rare variants in 43 genes associated with cardiomyopathy. Results were compared to two control groups: women with a gynecologic disorder and published data from the Exome Aggregation Consortium.


Of 181 women with preeclampsia, 96% were Caucasian, and 72% had at least one preterm preeclampsia delivery at <37 weeks. In the 43 cardiomyopathy genes studied in the subjects with preeclampsia, there were 10 rare loss-of-function variants and 228 rare damaging missense variants. These loss-of-function variants were more common in preeclampsia than local controls (5.5% vs. 2.5%, p = 0.014). At least one loss-of-function mutation or damaging missense variant was present in 68% of women with preeclampsia (mean 1.94 mutations). 55% of mutations occurred in the TTN gene. TTN mutations were present in 73% of women with preeclampsia versus 48% in local controls (p < 0.0001).


Gene mutations associated with cardiomyopathy (particularly in TTN) are more prevalent among women with preeclampsia.


The association between preeclampsia and peripartum cardiomyopathy has been previously observed clinically. This study adds new appreciation for shared gene mutations between preeclampsia and cardiomyopathy. The precise connections between various complex gene mutations and heterogeneous phenotypic presentations warrant additional research. Preeclampsia is also associated with increased long-term risk of cardiovascular disease. The potential for identifying gene mutations that could reliably risk stratify women is exciting and needs to be further explored.

Clinical Topics: Arrhythmias and Clinical EP, Heart Failure and Cardiomyopathies, Prevention, Genetic Arrhythmic Conditions, Acute Heart Failure

Keywords: Blood Pressure, Cardiomyopathies, DNA, Exome, Genetics, Heart Failure, Mutation, Peripartum Period, Pre-Eclampsia, Pregnancy, Secondary Prevention, Women

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