Researchers identify gene mutation that may cause peripartum cardiomyopathy

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Researchers have found the prevalence of truncating variants in genes was similar between women with peripartum cardiomyopathy and patients with dilated cardiomyopathy.

Two-thirds of the truncating variants were in their TTN gene, which is the largest protein in the body. Both populations had significantly more people with truncating variants compared with a control group.

Lead author James S. Ware, PhD, of Harvard Medical School in Boston, and colleagues published their results online in the  New England Journal of Medicine on Jan. 6.

“Until now, we had very little insight into the cause of peripartum cardiomyopathy,” Zoltan Arany, MD, PhD, the study’s senior author and an associate professor of Cardiovascular Medicine, said in a  news release. “There had been theories that it was linked to a viral infection, or paternal genes attacking the mother’s circulatory system, or just the stresses of pregnancy. However, this research shows that a mutation in the TTN gene is the cause of a significant number of peripartum cardiomyopathies, even in women without a family history of the disease.”

The researchers noted that the incidence of peripartum cardiomyopathy varies from 1 in 100 to 1 in 300 in geographic hot spots such as Nigeria and Haiti to 1 in 1,000 to 1 in 4,000 in the U.S. and Europe. Although the cause of peripartum cardiomyopathy is not known, risk factors include the presence of preeclampsia, twin gestation and advanced maternal age.

Meanwhile, previous studies found that gene mutations cause idiopathic dilated cardiomyopathy, which the researchers noted shares some clinical features with peripartum cardiomyopathy such as decreased systolic function, enlarged cardiac dimensions and nonspecific histologic findings on biopsy.

In this study, the researchers enrolled 172 women with peripartum cardiomyopathy and sequenced DNA from them to evaluate the contribution of variants in 43 genes that were previously shown to be associated with dilated cardiomyopathy.

The mean age of the women was 31.3 years old, while 35 percent were of African descent, which the researchers said was consistent with the prevalence of peripartum cardiomyopathy among that population.

Of the 172 women, 26 carried 26 rare heterozygous truncating variants in eight genes. Truncating variants were found in 15 percent of women with peripartum cardiomyopathy compared with 4.7 percent among a reference population of more than 60,000 samples and 17 percent of a cohort of patients with dilated cardiomyopathy.

Of the 26 truncating variants, 65 percent affected the TTN gene. The researchers mentioned that 13 percent of women of African descent and 8 percent of women of European descent had TTN truncating variants.

Further, they said that four of the TTN truncating variants were the same as variants previously identified in 26 patients with dilated cardiomyopathy at Brigham and Women’s Hospital in Boston.

“We conclude that peripartum cardiomyopathy shares a genetic predisposition with both familial and sporadic idiopathic dilated cardiomyopathy,” they wrote.