Cardiomyopathy and Preeclampsia.

Area of Science:

• Cardiovascular Genetics
• Reproductive Medicine
• Genomic Medicine

Background:

• Preeclampsia is associated with maternal cardiovascular diseases, including diastolic dysfunction and cardiomyopathy.
• Gene mutations linked to idiopathic cardiomyopathy have been implicated in peripartum cardiomyopathy.
• The role of cardiomyopathy gene mutations in preeclampsia remains unclear.

Purpose of the Study:

• To investigate whether cardiomyopathy gene mutations contribute to the development of preeclampsia.
• To identify specific gene variants associated with preeclampsia in a patient cohort.

Main Methods:

• Whole exome sequencing was performed on 181 preeclampsia subjects and compared to control groups.
• Rare variants (MAF <0.1%) in 43 cardiomyopathy genes were analyzed.
• Loss-of-function and damaging missense variants were identified and quantified.

Main Results:

• Preeclampsia subjects showed a significantly higher prevalence of rare loss-of-function variants (5.5% vs 2.5%) in cardiomyopathy genes compared to controls (P=0.014).
• Sixty-eight percent of preeclampsia patients carried at least one loss-of-function or damaging missense variant.
• The TTN gene harbored the majority of mutations (55%), with 73% of preeclampsia subjects having TTN mutations versus 48% in controls (P=1.36E-11).

Conclusions:

• Women with preeclampsia are more likely to carry protein-altering mutations in cardiomyopathy-associated genes, particularly TTN.
• These mutations are prevalent across preeclampsia, idiopathic cardiomyopathy, and peripartum cardiomyopathy, indicating a broader role in cardiovascular disorders.
• Identifying these variants can improve diagnosis, classification, counseling, and management of at-risk women.