Molecular Biology Reports

, Volume 39, Issue 1, pp 221–226

A meta-analysis of HLA-DR polymorphism and genetic susceptibility to idiopathic dilated cardiomyopathy

  • Bo Jin
  • Xin-Ping Luo
  • Huan-Chun Ni
  • Wei Shen
  • Hai-Ming Shi
  • Yong Li


Idiopathic dilated cardiomyopathy (IDC) has been hypothesized as a multifactorial disorder initiated by an environment trigger in individuals with predisposing human leukocyte antigen (HLA) alleles. Published data on the association between HLA-DR polymorphism and IDC risk are inconclusive. To derive a more precise estimation of the relationship, a meta-analysis was performed. A total of 19 case–control studies including 1,378 cases and 10,383 controls provided data on the association between HLA-DR polymorphism and genetic susceptibility to IDC. Overall, statistically elevated frequencies of HLA-DR4 (OR 1.58; 95% CI 1.21–2.07; P = 0.0009) and HLA-DR5 (OR 1.35; 95% CI 1.05–1.73; P = 0.02) alleles were found in patients with IDC compared with controls. Individuals with HLA-DR3 antigen have a protective effect against IDC (OR 0.72; 95% CI 0.58–0.90; P = 0.004). In summary, this meta-analysis indicated that certain HLA-DR alleles may be genetic markers for susceptibility and resistance to IDC.


HLA-DR Dilated cardiomyopathy Polymorphism Meta-analysis 

Supplementary material

11033_2011_729_MOESM1_ESM.doc (32 kb)
Supplementary material 1 (DOC 32 kb)


  1. 1.
    Dec GW, Fuster V (1994) Idiopathic dilated cardiomyopathy. N Engl J Med 331:1564–1575PubMedCrossRefGoogle Scholar
  2. 2.
    Bender JR (1991) Idiopathic dilated cardiomyopathy. An immunologic, genetic, or infectious disease, or all of the above? Circulation 83:704–706PubMedGoogle Scholar
  3. 3.
    Agarwal AK, White AG, Ali M, Leheny WA, Daar AS (1996) HLA antigens in an Omani population with dilated cardiomyopathy. Int J Cardiol 55:29–32PubMedCrossRefGoogle Scholar
  4. 4.
    Anderson JL, Carlquist JF, Lutz JR, DeWitt CW, Hammond EH (1984) HLA A, B and DR typing in idiopathic dilated cardiomyopathy: a search for immune response factors. Am J Cardiol 53:1326–1330PubMedCrossRefGoogle Scholar
  5. 5.
    Arbustini E, Gavazzi A, Pozzi R, Grasso M, Pucci A, Campana C, Graziano G, Martinetti M, Cuccia M, Salvaneschi L (1989) The morphologic spectrum of dilated cardiomyopathy and its relation to immune-response genes. Am J Cardiol 64:991–995PubMedCrossRefGoogle Scholar
  6. 6.
    Caforio AL, Martinetti M, Schwarz G, Bonifacio E, Gavazzi A, Graziano G, Lorini R, Cuccia M, McKenna WJ, Bottazzo GF (1992) Idiopathic dilated cardiomyopathy: lack of association between circulating organ-specific cardiac antibodies and HLA-DR antigens. Tissue Antigens 39:236–240PubMedCrossRefGoogle Scholar
  7. 7.
    Carlquist JF, Menlove RL, Murray MB, O’Connell JB, Anderson JL (1991) HLA class II (DR and DQ) antigen associations in idiopathic dilated cardiomyopathy. Validation study and meta-analysis of published HLA association studies. Circulation 83:515–522PubMedGoogle Scholar
  8. 8.
    Carlquist JF, Ward RH, Husebye D, Feolo M, Anderson JL (1994) Major histocompatibility complex class II gene frequencies by serologic and deoxyribonucleic acid genomic typing in idiopathic dilated cardiomyopathy. Am J Cardiol 74:918–920PubMedCrossRefGoogle Scholar
  9. 9.
    Grant SC, Sheldon S, Dyer PA, Levy RD, Brooks NH (1994) Do specific HLA antigens predispose to ischaemic heart disease or idiopathic dilated cardiomyopathy? Br Heart J 71:76–78PubMedCrossRefGoogle Scholar
  10. 10.
    Harcombe AA, Sharples L, Large SR, Wallwork J, Weissberg PL, Joysey V (1999) HLA antigen frequencies in end-stage idiopathic and ischaemic cardiomyopathy. Int J Cardiol 68:31–37PubMedCrossRefGoogle Scholar
  11. 11.
    Komajda M, Raffoux C, Salame E, Colombani J, Grosgogeat Y, Cabrol C, Dausset J (1987) HLA A-B and DR in dilated myocardiopathies. Arch Mal Coeur Vaiss 80:1233–1237PubMedGoogle Scholar
  12. 12.
    Limas CJ, Limas C (1989) HLA antigens in idiopathic dilated cardiomyopathy. Br Heart J 62:379–383PubMedCrossRefGoogle Scholar
  13. 13.
    Liu W, Li WM, Yang SS, Gao C, Li SJ, Li Y, Kong YH, Gan RT (2006) Association of HLA class II DRB1, DPA1 and DPB1 polymorphism with genetic susceptibility to idiopathic dilated cardiomyopathy in Chinese Han nationality. Autoimmunity 39:461–467PubMedCrossRefGoogle Scholar
  14. 14.
    Lozano MD, Rubocki RJ, Wilson JE, McManus BM, Wisecarver JL (1997) Human leukocyte antigen class II associations in patients with idiopathic dilated cardiomyopathy. Myocarditis treatment trial investigators. J Card Fail 3:97–103PubMedCrossRefGoogle Scholar
  15. 15.
    Mahjoub S, Mehri S, Ghazouani E, Ouarda F, Boussada R, Zaroui A, Mechmeche R, Hammami M, Ben Arab S (2010) HLA class II polymorphisms in Tunisian patients with dilated cardiomyopathy. Tissue Antigens 75:679–683PubMedCrossRefGoogle Scholar
  16. 16.
    Maharaj B, Hammond MG (1990) HLA-A, B, DR, and DQ antigens in black patients with idiopathic dilated cardiomyopathy. Am J Cardiol 65:1402–1403PubMedCrossRefGoogle Scholar
  17. 17.
    Nishi H, Koga Y, Koyanagi T, Harada H, Imaizumi T, Toshima H, Sasazuki T, Kimura A (1995) DNA typing of HLA class II genes in Japanese patients with dilated cardiomyopathy. J Mol Cell Cardiol 27:2385–2392PubMedCrossRefGoogle Scholar
  18. 18.
    Osa A, Almenar L, Palencia M, Puig N, Chirivella M, Montoro J (1999) Antigens of the major histocompatibility system in ischemic heart disease and idiopathic dilated cardiomyopathy. Clin Cardiol 22:292–296PubMedCrossRefGoogle Scholar
  19. 19.
    Rodríguez-Pérez JM, Fragoso JM, Alvarez-León E, Martínez-Rodríguez N, Gallardo GJ, Inés-Real S, Granados J, Reyes PA, Vargas-Alarcón G (2007) MHC class II genes in Mexican patients with idiopathic dilated cardiomyopathy. Exp Mol Pathol 82:49–52PubMedCrossRefGoogle Scholar
  20. 20.
    Wang Q, Liao Y, Gong F, Mao H, Zhang J (2000) HLA-DRB1 gene polymorphism in patients with dilated cardiomyopathy. J Tongji Med Univ 20:141–142PubMedCrossRefGoogle Scholar
  21. 21.
    Zerbe TR, Kaufmann C, Colson Y, Duquesnoy R (1988) Associations of HLA-A, B, DR antigens with primary disease in cardiac allograft recipients. Am J Cardiol 61:1359–1361PubMedCrossRefGoogle Scholar
  22. 22.
    World Health Organization (1980) Report of the WHO/ISFC task force on the definition and classification of cardiomyopathies. Br Heart J 44:672–673CrossRefGoogle Scholar
  23. 23.
    Richardson P, McKenna W, Bristow M, Maisch B, Mautner B, O’Connell J, Olsen E, Thiene G, Goodwin J, Gyarfas I, Martin I, Nordet P (1996) Report of the 1995 World Health Organization/International Society and Federation of Cardiology Task Force on the Definition and Classification of cardiomyopathies. Circulation 93:841–842PubMedCrossRefGoogle Scholar
  24. 24.
    Higgins JP, Thompson SG (2002) Quantifying heterogeneity in a meta-analysis. Stat Med 21:1539–1558PubMedCrossRefGoogle Scholar
  25. 25.
    Tomer Y (2010) Genetic susceptibility to autoimmune thyroid disease: past, present, and future. Thyroid 20:715–725PubMedCrossRefGoogle Scholar
  26. 26.
    Limas CJ, Limas C, Kubo SH, Olivari MT (1990) Anti-beta-receptor antibodies in human dilated cardiomyopathy and correlation with HLA-DR antigens. Am J Cardiol 65:483–487PubMedCrossRefGoogle Scholar
  27. 27.
    Caforio AL, Mahon NJ, Tona F, McKenna WJ (2002) Circulating cardiac autoantibodies in dilated cardiomyopathy and myocarditis: pathogenetic and clinical significance. Eur J Heart Fail 4:411–417PubMedCrossRefGoogle Scholar
  28. 28.
    Villar J, Piaggio G (2005) Large trials or meta-analysis? That is not the question. Best Pract Res Clin Obstet Gynaecol 19:27–35PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media B.V. 2011

Authors and Affiliations

  • Bo Jin
    • 1
  • Xin-Ping Luo
    • 1
  • Huan-Chun Ni
    • 1
  • Wei Shen
    • 1
  • Hai-Ming Shi
    • 1
  • Yong Li
    • 1
  1. 1.Department of CardiologyHuashan Hospital, Fudan UniversityShanghaiChina

Personalised recommendations