Skip to main content
Log in

Association between polymorphism of MTHFR c.677C>T and risk of cardiovascular disease in Turkish population: a meta-analysis for 2.780 cases and 3.022 controls

  • Published:
Molecular Biology Reports Aims and scope Submit manuscript

Abstract

Cardiovascular diseases (CVDs) remain the main cause of morbidity and mortality around the world. A common polymorphism c.677C>T has been identified in the gene coding for methylenetetrahydrofolate reductase (MTHFR), which is involved in the remethylation of homocysteine, and may predispose to CVDs. A meta-analysis was performed to estimate the risk of CVDs associated with MTHFR c.677C>T in Turkish population. Published studies were retrieved from PubMed, Science Citation Index/Expanded, Google Scholar, Turkish Medline, and the Turkish Council of Higher Education Theses Database. For each study, we calculated odds ratios and 95 % confidence intervals (CI), assuming frequency of allele and homozygote comparison, dominant and recessive genetic models. Thirty-one separate studies were included and 2.780 cases/3.022 controls were involved in the current meta-analysis. Significant association was found between c.677C>T polymorphism and risk of CVD when all studies pooled with random-effects model for T versus C (OR 1.33; 95 % CI 1.11–1.59; p = 0.002), TT vs. CC (OR 1.87; 95 % CI 1.35–2.60; p = 3.53E−04), TT+CT vs. CC (OR 1.32; 95 % CI 1.06–1.64; p = 0.014) and TT vs. CT+CC (OR 1.75; 95 % CI 1.29–2.37; p = 6.57E−04). Further analysis indicated the significant association between methylenetetrahydrofolate reductase (MTHFR) TT genotype and groups with venous thrombosis, peripheral arterial thrombosis, acute MI/MI. No publication bias was observed in any comparison model. Our results of meta-analysis suggest that MTHFR c.677C>T polymorphism is associated with the CVDs in Turkish population.

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

Access this article

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
Fig. 5

Similar content being viewed by others

References

  1. Mendis S (2007) Prevention of cardiovascular disease in low resource settings. Eur J Cardiovasc Prev Rehabil 14(5):587–588

    Article  PubMed  Google Scholar 

  2. Nygard O, Nordrehaug JE, Refsum H, Ueland PM, Farstad M, Vollset SE (1997) Plasma homocysteine levels and mortality in patients with coronary artery disease. N Engl J Med 337(4):230–236

    Article  CAS  PubMed  Google Scholar 

  3. Rogers EJ, Chen S, Chan A (2007) Folate deficiency and plasma homocysteine during increased oxidative stress. N Engl J Med 357(4):421–422

    Article  CAS  PubMed  Google Scholar 

  4. Frosst P, Blom HJ, Milos R, Goyette P, Sheppard CA, Matthews RG, Boers GJ, den Heijer M, Kluijtmans LA, van den Heuvel LP et al (1995) A candidate genetic risk factor for vascular disease: a common mutation in methylenetetrahydrofolate reductase. Nat Genet 10(1):111–113

    Article  CAS  PubMed  Google Scholar 

  5. Harmon DL, Woodside JV, Yarnell JW, McMaster D, Young IS, McCrum EE, Gey KF, Whitehead AS, Evans AE (1996) The common ‘thermolabile’ variant of methylene tetrahydrofolate reductase is a major determinant of mild hyperhomocysteinaemia. QJM 89(8):571–577

    Article  CAS  PubMed  Google Scholar 

  6. Kerkeni M, Addad F, Chauffert M, Myara A, Gerhardt M, Chevenne D, Trivin F, Farhat MB, Miled A, Maaroufi K (2006) Hyperhomocysteinaemia, methylenetetrahydrofolate reductase polymorphism and risk of coronary artery disease. Ann Clin Biochem 43(Pt 3):200–206

    Article  CAS  PubMed  Google Scholar 

  7. Rozen R (1996) Molecular genetics of methylenetetrahydrofolate reductase deficiency. J Inherit Metab Dis 19(5):589–594

    Article  CAS  PubMed  Google Scholar 

  8. Kılbas A (2007) Investigation of prothrombic gene mutations in young patients with cerebral infarct. Master thesis, Süleyman Demirel University, Department of Biochemistry

  9. Agirbasli M, Guney AI, Ozturhan HS, Agirbasli D, Ulucan K, Sevinc D, Kirac D, Ryckman KK, Williams SM (2011) Multifactor dimensionality reduction analysis of MTHFR, PAI-1, ACE, PON1, and eNOS gene polymorphisms in patients with early onset coronary artery disease. Eur J Cardiovasc Prev Rehabil 18(6):803–809

    CAS  PubMed  Google Scholar 

  10. Celiker G, Can U, Verdi H, Yazici AC, Ozbek N, Atac FB (2009) Prevalence of thrombophilic mutations and ACE I/D polymorphism in Turkish ischemic stroke patients. Clin Appl Thromb Hemost 15(4):415–420

    Article  CAS  PubMed  Google Scholar 

  11. Kanadası M, Dönmez Y, Çaylı M, Demirtas M, Tanrıverdi K, Demir M, Alhan C (2008) Methylenetetrahydrofolate reductase gene polymorphism, homocysteine and folate levels in young patients with myocardial infarction. Türk Girişimsel Kard Der 12:26–31

    Google Scholar 

  12. Ucar F, Celik S, Yucel B, Sonmez M, Celep F, Erkut N (2011) MTHFR C677T polymorphism and its relationship to myocardial infarction in the Eastern Black Sea region of Turkey. Arch Med Res 42(8):709–712

    Article  CAS  PubMed  Google Scholar 

  13. Var A, Utuk O, Akcali S, Sanlidag T, Uyanik BS, Dinc G (2009) Impact of hemostatic gene single point mutations in patients with non-diabetic coronary artery disease. Mol Biol Rep 36(8):2235–2243

    Article  CAS  PubMed  Google Scholar 

  14. Pereira TV, Patsopoulos NA, Salanti G, Ioannidis JPA (2010) Critical interpretation of Cochran’s Q test depends on power and prior assumptions about heterogeneity. Res Syn Meth 1:149–161

    Article  Google Scholar 

  15. Higgins JP, Thompson SG, Deeks JJ, Altman DG (2003) Measuring inconsistency in meta-analyses. BMJ 327(7414):557–560

    Article  PubMed  Google Scholar 

  16. Walker E, Hernandez AV, Kattan MW (2008) Meta-analysis: its strengths and limitations. Cleve Clin J Med 75(6):431–439

    Article  PubMed  Google Scholar 

  17. DerSimonian R, Laird N (1986) Meta-analysis in clinical trials. Control Clin Trials 7(3):177–188

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  19. 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  PubMed  Google Scholar 

  20. Gonzalez-Perez E, Via M, Lopez-Alomar A, Esteban E, Valveny N, Bao M, Domingo E, Moral P (2002) Lack of association between methylenetetrahydrofolate reductase (MTHFR) C677T and ischaemic heart disease (IHD): family-based association study in a Spanish population. Clin Genet 62(3):235–239

    Article  CAS  PubMed  Google Scholar 

  21. Akar N, Akar E, Misirlioglu M, Avcu F, Yalcin A, Cin S (1998) Search for genetic factors favoring thrombosis in Turkish population. Thromb Res 92(2):79–82

    Article  CAS  PubMed  Google Scholar 

  22. Tokgozoglu SL, Alikasifoglu M, Atalar E, Unsal I, Aytemir K, Ozer N, Ovunc K, Usal O, Kes S, Tuncbilek E (1999) Methylene tetrahydrofolate reductase genotype and the risk and extent of coronary artery disease in a population with low plasma folate. Heart 81(5):518–522

    Google Scholar 

  23. Akar N, Akar E, Akcay R, Avcu F, Yalcin A, Cin S (2000) Effect of methylenetetrahydrofolate reductase 677 C-T, 1298 A-C, and 1317 T-C on factor V 1691 mutation in Turkish deep vein thrombosis patients. Thromb Res 97(3):163–167

    Article  CAS  PubMed  Google Scholar 

  24. Gulec S, Aras O, Akar E, Tutar E, Omurlu K, Avci F, Dincer I, Akar N, Oral D (2001) Methylenetetrahydrofolate reductase gene polymorphism and risk of premature myocardial infarction. Clin Cardiol 24(4):281–284

    Article  CAS  PubMed  Google Scholar 

  25. Ucar F, Sonmez M, Ovali E, Ozmenoglu M, Karti SS, Yilmaz M, Pakdemir A (2004) MTHFR C677T polymorphism and its relation to ischemic stroke in the Black Sea Turkish population. Am J Hematol 76(1):40–43

    Article  PubMed  Google Scholar 

  26. Agaoglu N, Turkyilmaz S, Ovali E, Ucar F, Agaoglu C (2005) Prevalence of prothrombotic abnormalities in patients with acute mesenteric ischemia. World J Surg 29(9):1135–1138

    Article  PubMed  Google Scholar 

  27. Yilmaz H, Isbir S, Agachan B, Ergen A, Farsak B, Isbir T (2006) C677T mutation of methylenetetrahydrofolate reductase gene and serum homocysteine levels in Turkish patients with coronary artery disease. Cell Biochem Funct 24(1):87–90

    Article  CAS  PubMed  Google Scholar 

  28. Sazci A, Ergul E, Tuncer N, Akpinar G, Kara I (2006) Methylenetetrahydrofolate reductase gene polymorphisms are associated with ischemic and hemorrhagic stroke: dual effect of MTHFR polymorphisms C677T and A1298C. Brain Res Bull 71(1–3):45–50

    Article  CAS  PubMed  Google Scholar 

  29. Dikmen M, Ozbabalik D, Gunes HV, Degirmenci I, Bal C, Ozdemir G, Basaran A (2006) Acute stroke in relation to homocysteine and methylenetetrahydrofolate reductase gene polymorphisms. Acta Neurol Scand 113(5):307–314

    Article  CAS  PubMed  Google Scholar 

  30. Dolek B, Eraslan S, Eroglu S, Kesim BE, Ulutin T, Yalciner A, Laleli YR, Gozukirmizi N (2007) Molecular analysis of factor V Leiden, factor V Hong Kong, factor II G20210A, methylenetetrahydrofolate reductase C677T, and A1298C mutations related to Turkish thrombosis patients. Clin Appl Thromb Hemost 13(4):435–438

    Article  CAS  PubMed  Google Scholar 

  31. Taymaz H, Erarslan S, Oner ET, Alkan T, Agirbasli M, Kirdar B (2007) Sequence variations within the genes related to hemostatic imbalance and their impact on coronary artery disease in Turkish population. Thromb Res 119(1):55–62

    Article  CAS  PubMed  Google Scholar 

  32. Ozyurek E, Balta G, Degerliyurt A, Parlak H, Aysun S, Gurgey A (2007) Significance of factor V, prothrombin, MTHFR, and PAI-1 genotypes in childhood cerebral thrombosis. Clin Appl Thromb Hemost 13(2):154–160

    Article  CAS  PubMed  Google Scholar 

  33. Celik M, Altintas A, Celik Y, Karabulut A, Ayyildiz O (2008) Thrombophilia in young patients with acute myocardial infarction. Saudi Med J 29(1):48–54

    PubMed  Google Scholar 

  34. Caner M, Bircan R, Sevinç D, Benli F, Güney AI, Kurtoglu N (2008) MTHFR, prothrombin and Factor V gene variants in Turkish patients with coronary artery stenosis. Genet Mol Biol 31(4):836–838

    Article  CAS  Google Scholar 

  35. Ilhan N, Kucuksu M, Kaman D, Ozbay Y (2008) The 677 C/T MTHFR polymorphism is associated with essential hypertension, coronary artery disease, and higher homocysteine levels. Arch Med Res 39(1):125–130

    Article  CAS  PubMed  Google Scholar 

  36. Akyıldız A (2008) Comparison of the calcium score and MTHFR, ACE, Factor-V gene mutations in coronary artery disease. Master thesis, Cumhuriyet University, Department of Radiology

  37. Bayan K, Tuzun Y, Yilmaz S, Canoruc N, Dursun M (2009) Analysis of inherited thrombophilic mutations and natural anticoagulant deficiency in patients with idiopathic portal hypertension. J Thromb Thrombolysis 28(1):57–62

    Article  CAS  PubMed  Google Scholar 

  38. Aydin M, Gokkusu C, Ozkok E, Tulubas F, Unlucerci Y, Pamukcu B, Ozbek Z, Umman B (2009) Association of genetic variants in methylenetetrahydrofolate reductase and paraoxonase-1 genes with homocysteine, folate and vitamin B12 in coronary artery disease. Mol Cell Biochem 325(1–2):199–208

    Article  CAS  PubMed  Google Scholar 

  39. Izmirli M, Alptekin D, Topçuoğlu MŞ, Güzel AI (2009) Investigation of methylene tetrahydrofolate reductase gene polymorphisms in coronary by-passed patients due to coronary atherosclerosis etiology. Turkiye Klinikleri J Cardiovasc Sci 21(3):303–308

    Google Scholar 

  40. Ozen F, Manduz Ş, Katrancıoğlu N, Karahan O, Köksal B, Ozdemir O (2009) Role of prothrombotic gene polymorphism in patients with thromboangiitis obliterans. Turkiye Klinikleri J Cardiovasc Sci 21(2):160–164

    Google Scholar 

  41. Ozmen F, Ozmen MM, Ozalp N, Akar N (2009) The prevalence of factor V (G1691A), MTHFR (C677T) and PT (G20210A) gene mutations in arterial thrombosis. Ulus Travma Acil Cerrahi Derg 15(2):113–119

    PubMed  Google Scholar 

  42. Bolaman Z, Ozkul A, Kiylioglu N, Kadikoylu G, Erturk A, Batun S, Akyol A (2009) Hereditary thrombophilic factors in stroke due to cerebral infarct. Am J Med Sci 337(1):11–13

    Article  PubMed  Google Scholar 

  43. Hanta I, Soydas Y, Karatasli M, Koseoglu Z, Satar S, Hasturk S (2010) Plasma homocysteine level and 677C --> T mutation on the MTHFR gene in patients with venous thromboembolism. Bratisl Lek Listy 111(2):70–73

    CAS  PubMed  Google Scholar 

  44. Kupeli E, Verdi H, Simsek A, Atac FB, Eyuboglu FO (2011) Genetic mutations in Turkish population with pulmonary embolism and deep venous thrombosis. Clin Appl Thromb Hemost 17(6):E87–E94

    Article  PubMed  Google Scholar 

  45. Alioglu E, Turk U, Cam S, Abbasaliyev A, Tengiz I, Ercan E (2009) Polymorphisms of the methylenetetrahydrofolate reductase, vascular endothelial growth factor, endothelial nitric oxide synthase, monocyte chemoattractant protein-1 and apolipoprotein E genes are not associated with carotid intima-media thickness. Can J Cardiol 25(1):e1–e5

    Article  CAS  PubMed  Google Scholar 

  46. Erkan O, Bozdayi AM, Disibeyaz S, Oguz D, Ozcan M, Bahar K, Karayalcin S, Ozden A, Bozkaya H, Yurdaydin C, Uzunalimoglu O (2005) Thrombophilic gene mutations in cirrhotic patients with portal vein thrombosis. Eur J Gastroenterol Hepatol 17(3):339–343

    Article  CAS  PubMed  Google Scholar 

  47. Tug E, Aydin H, Kaplan E, Dogruer D (2011) Frequency of genetic mutations associated with thromboembolism in the Western Black Sea Region. Intern Med 50(1):17–21

    Article  CAS  PubMed  Google Scholar 

  48. Ozbek N, Alioglu B, Avci Z, Malbora B, Onay O, Ozyurek E, Atac FB (2009) Incidence of and risk factors for childhood thrombosis: a single-center experience in Ankara, Turkey. Pediatr Hematol Oncol 26(1):11–29

    Article  CAS  PubMed  Google Scholar 

  49. Arslan S, Manduz S, Epozturk K, Karahan O, Akkurt I (2011) Association of deep venous thrombosis with prothrombotic gene polymorphism identified in lung cancer cases. Mol Biol Rep 38(4):2395–2400

    Article  CAS  PubMed  Google Scholar 

  50. Sahin S, Benli I, Aydogan L (2012) Distribution of prothrombin G20210A, factor V Leiden, and MTHFR C677T mutations in the middle Black Sea area (Tokat) of Turkey. Turk J Med Sci 42(6):1093–1097

    CAS  Google Scholar 

  51. Yokus O, Albayrak M, Balcik OS, Ceran F, Dagdas S, Yilmaz M, Ozet G (2009) Risk factors for thrombophilia in young adults presenting with thrombosis. Int J Hematol 90(5):583–590

    Article  CAS  PubMed  Google Scholar 

  52. Onrat ST, Akci O, Soylemez Z, Onrat E, Avsar A (2012) Prevalence of myocardial infarction polymorphisms in Afyonkarahisar, Western Turkey. Mol Biol Rep 39(9):9257–9264

    Article  CAS  PubMed  Google Scholar 

  53. Dinleyici EC, Kirel B, Alatas O, Muslumanoglu H, Kilic Z, Dogruel N (2006) Plasma total homocysteine levels in children with type 1 diabetes: relationship with vitamin status, methylene tetrahydrofolate reductase genotype, disease parameters and coronary risk factors. J Trop Pediatr 52(4):260–266

    Article  CAS  PubMed  Google Scholar 

  54. Yilmaz H, Agachan B, Ergen A, Karaalib ZE, Isbir T (2004) Methylene tetrahydrofolate reductase C677T mutation and left ventricular hypertrophy in Turkish patients with type II diabetes mellitus. J Biochem Mol Biol 37(2):234–238

    Article  CAS  PubMed  Google Scholar 

  55. Demirel Y, Dogan S, Uludag A, Silan C, Atik S, Silan F, Ozdemir O (2011) Combined effect of Factor V Leiden, MTHFR, and angiotensin-converting enzyme (insertion/deletion) gene mutations in hypertensive adult individuals: a population-based study from Sivas and Canakkale, Turkey. Genet Test Mol Biomarkers 15(11):785–791

    Article  CAS  PubMed  Google Scholar 

  56. Higgins J, Green Se (2011) cochrane handbook for systematic reviews of interventions version 5.1.0. The Cochrane Collaboration. www.cochrane-handbook.org. Updated March 2011

  57. Roger VL, Go AS, Lloyd-Jones DM, Benjamin EJ, Berry JD, Borden WB, Bravata DM, Dai S, Ford ES, Fox CS, Fullerton HJ, Gillespie C, Hailpern SM, Heit JA, Howard VJ, Kissela BM, Kittner SJ, Lackland DT, Lichtman JH, Lisabeth LD, Makuc DM, Marcus GM, Marelli A, Matchar DB, Moy CS, Mozaffarian D, Mussolino ME, Nichol G, Paynter NP, Soliman EZ, Sorlie PD, Sotoodehnia N, Turan TN, Virani SS, Wong ND, Woo D, Turner MB (2012) Heart disease and stroke statistics–2012 update: a report from the American Heart Association. Circulation 125(1):e2–e220

    Article  PubMed  Google Scholar 

  58. McCully KS (1996) Homocysteine and vascular disease. Nat Med 2(4):386–389

    Article  CAS  PubMed  Google Scholar 

  59. Steed MM, Tyagi SC (2011) Mechanisms of cardiovascular remodeling in hyperhomocysteinemia. Antioxid Redox Signal 15(7):1927–1943

    Article  CAS  PubMed  Google Scholar 

  60. Derici K, Samsar U, Demirel-Yilmaz E (2012) Nitric oxide effects depend on different mechanisms in different regions of the rat heart. Heart Vessels 27(1):89–97

    Article  PubMed  Google Scholar 

  61. Roje S, Chan SY, Kaplan F, Raymond RK, Horne DW, Appling DR, Hanson AD (2002) Metabolic engineering in yeast demonstrates that S-adenosylmethionine controls flux through the methylenetetrahydrofolate reductase reaction in vivo. J Biol Chem 277(6):4056–4061

    Article  CAS  PubMed  Google Scholar 

  62. Jang MJ, Jeon YJ, Choi WI, Choi YS, Kim SY, Chong SY, Oh D, Kim NK (2012) The 677C>T mutation of the MTHFR gene increases the risk of venous thromboembolism in Koreans and a meta-analysis from Asian population. Clin Appl Thromb Hemost. doi:10.1177/1076029612436677

    Google Scholar 

  63. Xuan C, Bai XY, Gao G, Yang Q, He GW (2011) Association between polymorphism of methylenetetrahydrofolate reductase (MTHFR) C677T and risk of myocardial infarction: a meta-analysis for 8,140 cases and 10,522 controls. Arch Med Res 42(8):677–685

    Article  CAS  PubMed  Google Scholar 

  64. Yang Q, Bailey L, Clarke R, Flanders WD, Liu T, Yesupriya A, Khoury MJ, Friedman JM (2012) Prospective study of methylenetetrahydrofolate reductase (MTHFR) variant C677T and risk of all-cause and cardiovascular disease mortality among 6,000 US adults. Am J Clin Nutr 95(5):1245–1253

    Article  CAS  PubMed  Google Scholar 

  65. Wald DS, Morris JK, Wald NJ (2011) Reconciling the evidence on serum homocysteine and ischaemic heart disease: a meta-analysis. PLoS One 6(2):e16473

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  66. Li YY (2012) Methylenetetrahydrofolate reductase C677T gene polymorphism and coronary artery disease in a Chinese Han population: a meta-analysis. Metabolism 61(6):846–852

    Article  CAS  PubMed  Google Scholar 

  67. Doshi SN, McDowell IF, Moat SJ, Payne N, Durrant HJ, Lewis MJ, Goodfellow J (2002) Folic acid improves endothelial function in coronary artery disease via mechanisms largely independent of homocysteine lowering. Circulation 105(1):22–26

    Article  CAS  PubMed  Google Scholar 

  68. Holmes MV, Newcombe P, Hubacek JA, Sofat R, Ricketts SL, Cooper J, Breteler MM, Bautista LE, Sharma P, Whittaker JC, Smeeth L, Fowkes FG, Algra A, Shmeleva V, Szolnoki Z, Roest M, Linnebank M, Zacho J, Nalls MA, Singleton AB, Ferrucci L, Hardy J, Worrall BB, Rich SS, Matarin M, Norman PE, Flicker L, Almeida OP, van Bockxmeer FM, Shimokata H, Khaw KT, Wareham NJ, Bobak M, Sterne JA, Smith GD, Talmud PJ, van Duijn C, Humphries SE, Price JF, Ebrahim S, Lawlor DA, Hankey GJ, Meschia JF, Sandhu MS, Hingorani AD, Casas JP (2011) Effect modification by population dietary folate on the association between MTHFR genotype, homocysteine, and stroke risk: a meta-analysis of genetic studies and randomised trials. Lancet 378(9791):584–594

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  69. Oner N, Vatansever U, Karasalihoglu S, Ekuklu G, Celtik C, Biner B (2006) The prevalence of folic acid deficiency among adolescent girls living in Edirne, Turkey. J Adolesc Health 38(5):599–606

    Article  PubMed  Google Scholar 

  70. Prengler M, Sturt N, Krywawych S, Surtees R, Liesner R, Kirkham F (2001) Homozygous thermolabile variant of the methylenetetrahydrofolate reductase gene: a potential risk factor for hyperhomocysteinaemia, CVD, and stroke in childhood. Dev Med Child Neurol 43(4):220–225

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

The authors wish to thank Prof. Dr. Meral Kayıkçıoğlu and Prof. Dr. M. Ziya Alkan (Ege University Medical Faculty) for helping us constructive criticism and contributions to the manuscript.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Vildan Bozok Çetintaş.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Bozok Çetintaş, V., Gündüz, C. Association between polymorphism of MTHFR c.677C>T and risk of cardiovascular disease in Turkish population: a meta-analysis for 2.780 cases and 3.022 controls. Mol Biol Rep 41, 397–409 (2014). https://doi.org/10.1007/s11033-013-2873-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11033-013-2873-z

Keywords

Navigation