Shared Genetic Predisposition in Peripartum and Dilated Cardiomyopathies
- PMID: 26735901
- PMCID: PMC4797319
- DOI: 10.1056/NEJMoa1505517
Shared Genetic Predisposition in Peripartum and Dilated Cardiomyopathies
Abstract
Background Peripartum cardiomyopathy shares some clinical features with idiopathic dilated cardiomyopathy, a disorder caused by mutations in more than 40 genes, including TTN, which encodes the sarcomere protein titin. Methods In 172 women with peripartum cardiomyopathy, we sequenced 43 genes with variants that have been associated with dilated cardiomyopathy. We compared the prevalence of different variant types (nonsense, frameshift, and splicing) in these women with the prevalence of such variants in persons with dilated cardiomyopathy and with population controls. Results We identified 26 distinct, rare truncating variants in eight genes among women with peripartum cardiomyopathy. The prevalence of truncating variants (26 in 172 [15%]) was significantly higher than that in a reference population of 60,706 persons (4.7%, P=1.3×10(-7)) but was similar to that in a cohort of patients with dilated cardiomyopathy (55 of 332 patients [17%], P=0.81). Two thirds of identified truncating variants were in TTN, as seen in 10% of the patients and in 1.4% of the reference population (P=2.7×10(-10)); almost all TTN variants were located in the titin A-band. Seven of the TTN truncating variants were previously reported in patients with idiopathic dilated cardiomyopathy. In a clinically well-characterized cohort of 83 women with peripartum cardiomyopathy, the presence of TTN truncating variants was significantly correlated with a lower ejection fraction at 1-year follow-up (P=0.005). Conclusions The distribution of truncating variants in a large series of women with peripartum cardiomyopathy was remarkably similar to that found in patients with idiopathic dilated cardiomyopathy. TTN truncating variants were the most prevalent genetic predisposition in each disorder.
Figures
![Figure 1](https://cdn.statically.io/img/www.ncbi.nlm.nih.gov/pmc/articles/instance/4797319/bin/nihms763003f1.gif)
Comment in
-
Cardiomyopathies: Genetic overlap between peripartum and dilated cardiomyopathies.Nat Rev Cardiol. 2016 Mar;13(3):121. doi: 10.1038/nrcardio.2016.3. Epub 2016 Jan 22. Nat Rev Cardiol. 2016. PMID: 26794013 No abstract available.
-
Shared Genetic Predisposition in Peripartum and Dilated Cardiomyopathies.N Engl J Med. 2016 Jun 30;374(26):2601-2. doi: 10.1056/NEJMc1602671. N Engl J Med. 2016. PMID: 27355546 No abstract available.
-
Shared Genetic Predisposition in Peripartum and Dilated Cardiomyopathies.N Engl J Med. 2016 Jun 30;374(26):2601. doi: 10.1056/NEJMc1602671. N Engl J Med. 2016. PMID: 27355547 No abstract available.
-
Shared Genetic Predisposition in Peripartum and Dilated Cardiomyopathies.N Engl J Med. 2016 Jun 30;374(26):2601. doi: 10.1056/NEJMc1602671. N Engl J Med. 2016. PMID: 27355548 No abstract available.
Similar articles
-
Cardiac MRI as an Imaging Tool in Titin Variant-Related Dilated Cardiomyopathy.Cardiovasc Revasc Med. 2023 Jul;52:86-93. doi: 10.1016/j.carrev.2023.03.001. Epub 2023 Mar 7. Cardiovasc Revasc Med. 2023. PMID: 36934006 Review.
-
Second Hits in Dilated Cardiomyopathy.Curr Cardiol Rep. 2020 Jan 24;22(2):8. doi: 10.1007/s11886-020-1260-3. Curr Cardiol Rep. 2020. PMID: 31980956 Review.
-
Shared Genetic Predisposition in Peripartum and Dilated Cardiomyopathies.N Engl J Med. 2016 Jun 30;374(26):2601. doi: 10.1056/NEJMc1602671. N Engl J Med. 2016. PMID: 27355548 No abstract available.
-
Shared Genetic Predisposition in Peripartum and Dilated Cardiomyopathies.N Engl J Med. 2016 Jun 30;374(26):2601. doi: 10.1056/NEJMc1602671. N Engl J Med. 2016. PMID: 27355547 No abstract available.
-
Shared Genetic Predisposition in Peripartum and Dilated Cardiomyopathies.N Engl J Med. 2016 Jun 30;374(26):2601-2. doi: 10.1056/NEJMc1602671. N Engl J Med. 2016. PMID: 27355546 No abstract available.
Cited by
-
Screening for dilated cardiomyopathy in immediate family members: to whom, how, when (and where).Eur Heart J Suppl. 2024 Apr 17;26(Suppl 1):i93-i98. doi: 10.1093/eurheartjsupp/suae024. eCollection 2024 Apr. Eur Heart J Suppl. 2024. PMID: 38784151 Free PMC article.
-
The Genetic Factors Influencing Cardiomyopathies and Heart Failure across the Allele Frequency Spectrum.J Cardiovasc Transl Res. 2024 May 21. doi: 10.1007/s12265-024-10520-y. Online ahead of print. J Cardiovasc Transl Res. 2024. PMID: 38771459 Review.
-
Precision therapy in dilated cardiomyopathy: Pipedream or paradigm shift?Camb Prism Precis Med. 2023 Nov 20;1:e34. doi: 10.1017/pcm.2023.24. eCollection 2023. Camb Prism Precis Med. 2023. PMID: 38550947 Free PMC article. Review.
-
The "arrhythmic" presentation of peripartum cardiomyopathy: case series and critical review of the literature.Front Cardiovasc Med. 2024 Mar 14;11:1362692. doi: 10.3389/fcvm.2024.1362692. eCollection 2024. Front Cardiovasc Med. 2024. PMID: 38550516 Free PMC article.
-
Cardiomyopathies in Women.Methodist Debakey Cardiovasc J. 2024 Mar 14;20(2):59-69. doi: 10.14797/mdcvj.1368. eCollection 2024. Methodist Debakey Cardiovasc J. 2024. PMID: 38495661 Free PMC article. Review.
References
-
- Elkayam U. Clinical characteristics of peripartum cardiomyopathy in the United States: diagnosis, prognosis, and management. J Am Coll Cardiol. 2011;58:659–670. - PubMed
-
- Sliwa K, Fett J, Elkayam U. Peripartum cardiomyopathy. Lancet. 2006;368:687–693. - PubMed
-
- Hilfiker-Kleiner D, Sliwa K. Pathophysiology and epidemiology of peripartum cardiomyopathy. Nat Rev Cardiol. 2014;11:364–370. - PubMed
-
- Hilfiker-Kleiner D, Kaminski K, Podewski E, et al. A cathepsin D-cleaved 16 kDa form of prolactin mediates postpartum cardiomyopathy. Cell. 2007;128:589–600. - PubMed
Publication types
MeSH terms
Substances
Grants and funding
- K08 HL109159/HL/NHLBI NIH HHS/United States
- FS/15/81/31817/BHF_/British Heart Foundation/United Kingdom
- HL88577/HL/NHLBI NIH HHS/United States
- HL094499/HL/NHLBI NIH HHS/United States
- R56 HL125420/HL/NHLBI NIH HHS/United States
- HL080494/HL/NHLBI NIH HHS/United States
- R01 HL080494/HL/NHLBI NIH HHS/United States
- R01 HL094499/HL/NHLBI NIH HHS/United States
- RC1 HL102429/HL/NHLBI NIH HHS/United States
- HL102429/HL/NHLBI NIH HHS/United States
- SP/10/10/28431/BHF_/British Heart Foundation/United Kingdom
- FS/13/13/29819/BHF_/British Heart Foundation/United Kingdom
- HHMI/Howard Hughes Medical Institute/United States
- R01 HL084553/HL/NHLBI NIH HHS/United States
- R01 HL088577/HL/NHLBI NIH HHS/United States
- MC_U120085815/MRC_/Medical Research Council/United Kingdom
LinkOut - more resources
Full Text Sources
Other Literature Sources
Medical