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Contribution of polymorphic variantsof TOMM40/APOE gene locuses to the development of early postoperativecognitive dysfunction in coronary artery bypass grafting

Authors: Trubnikova O.A.1, Ponasenko A.V.1, Kagan E.S.2, Salakhov R.R.1, Khutornaya M.V.1, Maleva O.V.1, Barbarash O.L.1

Company: 1 Research Institute for Complex Issues of Cardiovascular Diseases; Sosnovyy bul’var, 6, Kemerovo, 650002, Russian Federation;
 2 Kemerovo State University; ulitsa Krasnaya, 6, Kemerovo, 650043, Russian Federation

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DOI: https://doi.org/10.15275/kreatkard.2016.04.07

For citation: Trubnikova O.A., Ponasenko A.V., Kagan E.S., Salakhov R.R., Khutornaya M.V., Maleva O.V., Barbarash O.L. Contribution of polymorphic variantsof TOMM40/APOE gene locuses to the development of early postoperativecognitive dysfunction in coronary artery bypass grafting. Creative Cardiology. 2016; 10 (4): 324-335 (in Russ.)

Keywords: coronary artery bypass grafting locus gene TOMM40/APOE early postoperative cognitive dysfunction

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Abstract

Objective. Analysis of the frequency and the prognostic significance of polymorphic variants of TOMM40/APOE genes in the development of early postoperative cognitive dysfunction (POCD) in patients undergoing on-pump coronary artery bypass grafting (CABG).
Material and methods. The study included 137 male patients undergoing on-pump coronary artery bypass grafting who were divided into two groups: those with early POCD (n=84) and those without early POCD (n=53). Five polymorphic variants of TOMM40 gene (rs741780, rs1160985, rs157580, rs2075650, rs8106922) and two polymorphic variants of APOE gene (rs429358, rs7412) were identified in all patients.
Results. This study demonstrates that the selected TOMM40/APOE candidate genes present the prognostic significance in the development of early POCD. It was found that risky genotypes were APOE ε2/ε3, T/C rs1160985, G/G rs157580, as well as the G/G and A/G rs8106922 TOMM40, while the TOMM40 G/G rs2075650 polymorphism was identified as the protective genotype for the development of early POCD in patients after CABG.
Conclusion. Genetic factors may contribute to the development of early POCD in patients undergoing CABG. The predictive value of the polymorphic variants of genes APOE (ε2/ε3), and TOMM40 (rs1160985, rs157580, rs8106922, rs2075650) in the development of early POCD after CABG was demonstrated.

References

  1. Oshchepkova E.V. Mortality of the population due to cardiovascular diseases in the Russian Federation in 2001–2006 and the ways to reduce it. Kardiologiya. 2009; 2: 67–72 (in Russ.).
  2. Bockeria L.A., Golukhova E.Z., Vanichkin A.V., Polunina A.G., Lefterov N.P., Kazanovskaya S.N. Echocardiographic correlates with cognitive dysfunction after cardiac surgery. Kreativnaya kardiologiya. 2015; 4: 13–25 (in Russ.).
  3. Selnes O.A., McKhann G.M. Neurocognitive complications after coronary artery bypass surgery. Ann. Neurol. 2005; 57: 615–21.
  4. Kneebone C., Luszcz M.A., Baker R.A., Knight J.L. A syndromal analysis of neuropsychological outcome following coronary artery bypass graft surgery. J. Neurol. Neurosurg. Psychiatry. 2005; 76 (8): 1121–27.
  5. Steinmetz J., Christensen K.B., Lund T., Lund T., Rasmussen L.S. Long-term consequences of postoperative cognitive dysfunction. Anesthesiology. 2009; 110 (3): 548–55.
  6. Levin O.S. Diagnostics and treatment of dementia in clinical practice. Moscow: Medpress-inform; 2009 (in Russ.).
  7. Mustafina O.E., Shagisultanova E.I., Tuktarova I.A., Khusnutdinova E.K. Polymorphism of apolipoprotein E gene and risk of myocardial infarction development. Molekulyarnaya biologiya. 2002; 36 (6): 978–84 (in Russ.).
  8. SOFA Calculator. Sequential Organ Failure Assessment (SOFA) severity of illness score for hospital mortality. Available at: http://clincalc.com/ IcuMortality/SOFA.aspx (accessed 13 October 2016).
  9. Maniatis T., Frich E.H., Sehmbruk Dzh. Molecular cloning. Moscow: Mir; 1984 (in Russ.).
  10. Gubler E.V., Genkin A.A. Application of non-parametrical criteria of statistics in biomedical researches. Leningrad: Meditsina; 1973 (in Russ.).
  11. Tardiff B.E., Newman M.F., Saunders A.M., Strittmatter W.J., Blumenthal J.A., White W.D. et al. Preliminary report of a genetic basis for cognitive decline after cardiac operations. Ann. Thorac. Surg. 1997; 64: 715–20.
  12. Lelis R.G., Krieger J.E., Pereira A.C., Schmidt A.P., Carmona M.J., Oliveira S.A. et al. Apolipoprotein E4 genotype increases the risk of postoperative cognitive dysfunction in patients undergoing coronary artery bypass graft surgery. J. Cardiovasc. Surg. (Torino). 2006; 47 (4): 451–56.
  13. Silbert B.S., Evered L.A., Scott D.A., Cowie T.F. The apolipoprotein E epsilon4 allele is not associated with cognitive dysfunction in cardiac surgery. Ann. Thorac. Surg. 2008; 86: 841–47. 334 Креативная кардиология. 2016; 10 (4)
  14. Tagarakis G.I., Tsolaki-Tagaraki F., Tsolaki M., Diegeler A., Tsilimingas N.B., Papassotiropoulos A. The role of apolipoprotein E in cognitive decline and delirium after bypass heart operations. Am. J. Alzheimers Dis. Other Demen. 2007; 22 (3): 223–28.
  15. Potkin S.G., Guffanti G., Lakatos A., Turner J.A., Kruggel F., Fallon J.H. et al. Hippocampal atrophy as a quantitative trait in a genome-wide association study identifying novel susceptibility genes for Alzheimer's disease. PLoS One. 2009; 4 (8): 1–15.
  16. Lambert J.C., Heath S., Even G., Campion D., Sleegers K., Hiltunen M. et al. Genome wide association study identifies variants at CLU and CR1 associated with Alzheimer's disease. Nat. Genet. 2009; 41: 1094–99.
  17. Lutz M.W., Crenshaw D.G., Saunders A.M., Roses A.D. Genetic variation at a single locus and age of onset for Alzheimer's disease. Alzheimers Dement. 2010; 6: 125–31.
  18. Khoury M.J., Bertram L., Boffetta P., Butterworth A.S., Chanock S.J., Dolan S.M. et al. Genome-wide association studies field synopses, and the development of the knowledge base on genetic variation and human diseases. Am. J. Epidemiol. 2009; 170: 269–79.
  19. Middelberg R.P., Ferreira M.A., Henders A.K., Heath A.C., Madden P.A. et al. Genetic variants in LPL, OASL and TOMM40/APOE-C1-C2-C4 genes are associated with multiple cardiovascularrelated traits. BMC Med. Genet. 2011; 12: 123.
  20. Salakhov R.R., Kashtalap V.V., Makeeva O.A., Barbarash O.L. TOMM40 polymorphisms are associated with cardiovascular phenotypes. Eur. J. Hum. Geneti. 2011; 19 (2): 266.
  21. Johnson S.C., LaRue A., Hermann B.P., Xu G., Koscik R.L., Jonaitis E.M. et al. The effect of TOMM40 poly-T length on gray matter volume and cognition in middle-aged persons with APOE ε3/ε3 genotype. Alzheimers Dement. 2011; 7: 456–65.
  22. Brodbeck J., Miranda R.D., Freedman S.B. Weisgraber K.H., Mahley R.W., Huang Y. Apolipoprotein E4 impairs mitochondrial function and increases reactive oxygen species in neuronal cells. Alzheimers Dement. 2009; 5: 307.
  23. Evered L.A., Silbert B.S., Scott D.A., Maruff P., Laughton K.M., Volitakis I. et al. Plasma amyloid beta42 and amyloid beta40 levels are associated with early cognitive dysfunction after cardiac surgery. Ann. Thorac. Surg. 2009; 88 (5): 1426–32.

Chief Editor

Leo A. Bockeria, MD, PhD, DSc, Professor, Academician of Russian Academy of Sciences, President of Bakoulev National Medical Research Center for Cardiovascular Surgery


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