Skip to main content
SpringerLink
Log in

Prevalence of TTN mutations in patients with dilated cardiomyopathy

A meta-analysis

Prävalenz von TTN-Mutationen bei Patienten mit dilatativer Kardiomyopathie

Eine Metaanalyse

  • Review articles
  • Published:
Herz Aims and scope Submit manuscript

Abstract

A meta-analysis was performed to assess the prevalence of TTN mutations in patients with dilated cardiomyopathy (DCM). Prevalence point estimates and 95% confidence intervals were computed using the logit transformation formula. The prevalence of TTN mutations in patient with DCM, familial dilated cardiomyopathy (FDCM), and sporadic dilated cardiomyopathy (SDCM) was 0.17 (95% CI: 0.14–0.19), 0.23 (95% CI: 0.20–0.26), and 0.16 (95% CI: 0.12–0.21), respectively. No individual study had a marked influence on the pooled prevalence in the meta-analysis. Meta-regression analysis between the logit event for prevalence and sample size explained 32% of between-study variance (p < 0.05). Cumulative meta-analysis confirmed the influence of sample size on the reported prevalence among the different studies. In conclusion, the present analysis suggests that TTN mutations are familial in DCM patients. More attention should be paid to TTN mutations in clinical examinations.

Zusammenfassung

Eine Metaanalyse wurde durchgeführt, um die Prävalenz von TTN-Mutationen bei Patienten mit dilatativer Kardiomyopathie (DCM) zu erfassen. Prävalenz-Punktschätzung und 95 %-Konfidenzintervalle wurden unter Verwendung der Logit-Transformationsformel errechnet. Die Prävalenz von TTN-Mutationen bei DCM-Patienten betrug 0,17 (95 %-KI: 0,14–0,19), bei familiärer dilatativer Kardiomyopathie (FDCM) 0,23 (95 %-KI: 0,20–0,26) bzw. bei sporadischer dilatativer Kardiomyopathie (SDCM) 0,16 (95 %-KI: 0,12–0,21). Es gab keine einzelne Studie mit deutlichem Einfluss auf die gepoolte Prävalenz im Rahmen der Metaanalyse. Die Metaregressionsanalyse zwischen dem Logit-Ereignis für die Prävalenz und der Stichprobengröße erklärte 32 % der Varianz zwischen den Studien (p < 0,05). Die kumulative Metaanalyse bestätigte den Einfluss der Stichprobengröße auf die angegebene Prävalenz bei den verschiedenen Studien. Die Schlussfolgerung der vorliegenden Analyse war, dass TTN-Mutationen familiär gehäuft bei DCM-Patienten auftreten. Daher sollte mehr Aufmerksamkeit auf TTN-Mutationen bei der klinischen Untersuchung gelegt werden.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Richardson P, McKenna W, Bristow M et al (1996) Report of the 1995 World Health Organization/International Society and Federation of Cardiology Task Force on the Definition and Classification of cardiomyopathies. Circulation 93(5):841–842

    Article  CAS  Google Scholar 

  2. Menon SC, Olson TM, Michels VV (2008) Genetics of familial dilated cardiomyopathy. Prog Pediatr Cardiol 25(1):57–67. https://doi.org/10.1016/j.ppedcard.2007.11.013

    Article  Google Scholar 

  3. Elliott P, Andersson B, Arbustini E et al (2008) Classification of the cardiomyopathies: a position statement from the European Society Of Cardiology Working Group on Myocardial and Pericardial Diseases. Eur Heart J 29(2):270–276. https://doi.org/10.1093/eurheartj/ehm342

    Article  PubMed  Google Scholar 

  4. Jefferies JL, Towbin JA (2010) Dilated cardiomyopathy. Lancet 375(9716):752–762. https://doi.org/10.1016/S0140-6736(09)62023-7

    Article  PubMed  Google Scholar 

  5. Garcia-Pavia P, Cobo-Marcos M, Guzzo-Merello G et al (2013) Genetics in dilated cardiomyopathy. Biomark Med 7(4):517–533. https://doi.org/10.2217/bmm.13.77

    Article  CAS  PubMed  Google Scholar 

  6. Cho KW, Lee J, Kim Y (2016) Genetic variations leading to familial dilated cardiomyopathy. Mol Cells 39(10):722–727. https://doi.org/10.14348/molcells.2016.0061

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Garfinkel AC, Seidman JG, Seidman CE (2018) Genetic pathogenesis of hypertrophic and dilated cardiomyopathy. Heart Fail Clin 14(2):139–146. https://doi.org/10.1016/j.hfc.2017.12.004

    Article  PubMed  PubMed Central  Google Scholar 

  8. Kayvanpour E, Sedaghat-Hamedani F, Amr A et al (2017) Genotype-phenotype associations in dilated cardiomyopathy: meta-analysis on more than 8000 individuals. Clin Res Cardiol 106(2):127–139. https://doi.org/10.1007/s00392-016-1033-6

    Article  CAS  PubMed  Google Scholar 

  9. Petretta M, Pirozzi F, Sasso L, Paglia A, Bonaduce D (2011) Review and metaanalysis of the frequency of familial dilated cardiomyopathy. Am J Cardiol 108(8):1171–1176. https://doi.org/10.1016/j.amjcard.2011.06.022

    Article  PubMed  Google Scholar 

  10. Akinrinade O, Koskenvuo JW, Alastalo T‑P (2015) Prevalence of Titin truncating variants in general population. PLoS ONE. https://doi.org/10.1371/journal.pone.0145284

    Article  PubMed  PubMed Central  Google Scholar 

  11. Fatkin D, Huttner IG (2017) Titin-truncating mutations in dilated cardiomyopathy: the long and short of it. Curr Opin Cardiol. https://doi.org/10.1097/hco.0000000000000382

    Article  PubMed  Google Scholar 

  12. Herman DS, Lam L, Taylor MR et al (2012) Truncations of titin causing dilated cardiomyopathy. N Engl J Med 366(7):619–628. https://doi.org/10.1056/NEJMoa1110186

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Guo W, Bharmal SJ, Esbona K, Greaser ML (2010) Titin diversity-alternative splicing gone wild. J Biomed Biotechnol. https://doi.org/10.1155/2010/753675

    Article  PubMed  PubMed Central  Google Scholar 

  14. Fatkin D, Lam L, Herman DS et al (2016) Titin truncating mutations: a rare cause of dilated cardiomyopathy in the young. Prog Pediatr Cardiol 40:41–45. https://doi.org/10.1016/j.ppedcard.2016.01.003

    Article  Google Scholar 

  15. Hershberger RE, Siegfried JD (2011) Update 2011: clinical and genetic issues in familial dilated cardiomyopathy. J Am Coll Cardiol 57(16):1641–1649. https://doi.org/10.1016/j.jacc.2011.01.015

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Haas J, Frese KS, Peil B et al (2015) Atlas of the clinical genetics of human dilated cardiomyopathy. Eur Heart J 36(18):1123–U1143. https://doi.org/10.1093/eurheartj/ehu301

    Article  CAS  PubMed  Google Scholar 

  17. Alaa Rostom, Catherine Dubé, Ann Cranney et al. Celiac Disease. Rockville (MD): Agency for Healthcare Research and Quality (US); 2004 Sep. (Evidence Reports/Technology Assessments, No. 104.) Appendix D. Quality Assessment Forms. https://www.ncbi.nlm.nih.gov/books/NBK35149/.

  18. Egger M, Davey Smith G, Schneider M, Minder C (1997) Bias in meta-analysis detected by a simple, graphical test. BMJ 315(7109):629–634

    Article  CAS  Google Scholar 

  19. Begg CB, Mazumdar M (1994) Operating characteristics of a rank correlation test for publication bias. Biometrics 50(4):1088–1101

    Article  CAS  Google Scholar 

  20. Franaszczyk M, Chmielewski P, Truszkowska G et al (2017) Titin truncating variants in dilated cardiomyopathy—prevalence and genotype-phenotype correlations. PLoS ONE 12(1):e169007. https://doi.org/10.1371/journal.pone.0169007

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Akinrinade O, Ollila L, Vattulainen S et al (2015) Genetics and genotype-phenotype correlations in Finnish patients with dilated cardiomyopathy. Eur Heart J 36(34):2327–2337. https://doi.org/10.1093/eurheartj/ehv253

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Dal Ferro M, Stolfo D, Altinier A et al (2017) Association between mutation status and left ventricular reverse remodelling in dilated cardiomyopathy. Heart 103(21):1704–1710. https://doi.org/10.1136/heartjnl-2016-311017

    Article  CAS  Google Scholar 

  23. Klauke B, Gaertner-Rommel A, Schulz U et al (2017) High proportion of genetic cases in patients with advanced cardiomyopathy including a novel homozygous Plakophilin 2‑gene mutation. PLoS ONE 12(12):e189489. https://doi.org/10.1371/journal.pone.0189489

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Tayal U, Newsome S, Buchan R et al (2017) Phenotype and clinical outcomes of Titin cardiomyopathy. J Am Coll Cardiol 70(18):2264–2274. https://doi.org/10.1016/j.jacc.2017.08.063

    Article  PubMed  PubMed Central  Google Scholar 

  25. Felkin LE, Walsh R, Ware JS et al (2016) Recovery of cardiac function in cardiomyopathy caused by Titin truncation. JAMA Cardiol 1(2):234–235. https://doi.org/10.1001/jamacardio.2016.0208

    Article  PubMed  PubMed Central  Google Scholar 

  26. Roberts AM, Ware JS, Herman DS et al (2015) Integrated allelic, transcriptional, and phenomic dissection of the cardiac effects of titin truncations in health and disease. Sci Transl Med 7(270):270ra6. https://doi.org/10.1126/scitranslmed.3010134

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Tobita T, Nomura S, Fujita T et al (2018) Genetic basis of cardiomyopathy and the genotypes involved in prognosis and left ventricular reverse remodeling. Sci Rep 8(1):1998. https://doi.org/10.1038/s41598-018-20114-9

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Janin A, N’Guyen K, Habib G et al (2017) Truncating mutations on myofibrillar myopathies causing genes as prevalent molecular explanations on patients with dilated cardiomyopathy. Clin Genet 92(6):616–623. https://doi.org/10.1111/cge.13043

    Article  CAS  PubMed  Google Scholar 

  29. Pugh TJ, Kelly MA, Gowrisankar S et al (2014) The landscape of genetic variation in dilated cardiomyopathy as surveyed by clinical DNA sequencing. Genet Med 16(8):601–608. https://doi.org/10.1038/gim.2013.204

    Article  CAS  PubMed  Google Scholar 

  30. Siu BL, Niimura H, Osborne JA et al (1999) Familial dilated cardiomyopathy locus maps to chromosome 2q31. Circulation 99(8):1022–1026

    Article  CAS  Google Scholar 

  31. Gerull B, Atherton J, Geupel A et al (2006) Identification of a novel frameshift mutation in the giant muscle filament titin in a large Australian family with dilated cardiomyopathy. J Mol Med 84(6):478–483. https://doi.org/10.1007/s00109-006-0060-6

    Article  CAS  PubMed  Google Scholar 

  32. Gerull B, Gramlich M, Atherton J et al (2002) Mutations of TTN, encoding the giant muscle filament titin, cause familial dilated cardiomyopathy. Nat Genet 30(2):201–204. https://doi.org/10.1038/ng815

    Article  CAS  PubMed  Google Scholar 

  33. Moher D, Liberati A, Tetzlaff J, Altman DG, The PRISMA Group (2009) Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. Plos Med 6(6):e1000097. https://doi.org/10.1371/journal.pmed1000097

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Pediatrics, Shandong Provincial Hospital Affiliated to Shandong University, No. 324, Jingwuweiqi Rd, 250021, Jinan, China

    H.-J. Fang MM

  2. Department of Epidemiology, Shandong University School of Public Health, No.44, Wenhuaxi Rd, 250012, Jinan, China

    B.-P. Liu MPH

Authors
  1. H.-J. Fang MM
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. B.-P. Liu MPH
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

Bao-Peng Liu and Hui-Juan Fang conceived of the study. Bao-Peng Liu and Hui-Juan participated in the data analysis. Bao-Peng Liu and Hui-Juan wrote, reviewed, and approved the final manuscript.

Corresponding author

Correspondence to B.-P. Liu MPH.

Ethics declarations

Conflict of interest

H.-J. Fang and B.-P. Liu declare that they have no competing interests.

For this article no studies with human participants or animals were performed by any of the authors. All studies performed were in accordance with the ethical standards indicated in each case.

Caption Electronic Supplementary Material

59_2019_4825_MOESM1_ESM.docx

Online Table 1 reports on the evaluation quality of the included studies. Online figures provide the results of sensitivity analyses.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Fang, HJ., Liu, BP. Prevalence of TTN mutations in patients with dilated cardiomyopathy. Herz 45 (Suppl 1), 29–36 (2020). https://doi.org/10.1007/s00059-019-4825-4

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00059-019-4825-4

Keywords

Schlüsselwörter

Search

Navigation