Українська Русский English

ISSN 2522-9028 (Print)
ISSN 2522-9036 (Online)
DOI: https://doi.org/10.15407/fz

Fiziologichnyi Zhurnal

is a scientific journal issued by the

Bogomoletz Institute of Physiology
National Academy of Sciences of Ukraine

Editor-in-chief: V.F. Sagach

The journal was founded in 1955 as
1955 – 1977 "Fiziolohichnyi zhurnal" (ISSN 0015 – 3311)
1978 – 1993 "Fiziologicheskii zhurnal" (ISSN 0201 – 8489)
1994 – 2016 "Fiziolohichnyi zhurnal" (ISSN 0201 – 8489)
2017 – "Fiziolohichnyi zhurnal" (ISSN 2522-9028)

Fiziol. Zh. 2017; 63(1): 33-42


ANALYSIS OF γ-GLUTAMYL CARBOXYLASE GENE rs2592551 POLYMORPHISM ASSOCIATION WITH ISCHEMIC ATHEROTHROMBOTIC STROKE

Ye.I. Dubovyk, V.Yu. Harbuzova, O.A. Obukhova, A.V. Ataman

    Sumy State University, Ukraine
DOI: https://doi.org/10.15407/fz63.01.033

Abstract

The results of γ-glutamyl carboxylase gene rs2592551 polymorphism determining in 170 patients with ischemic atherothrombotic stroke and 124 subjects without acute cerebrovascular disease (control group) have been evaluated. Obtained results revealed that rs2592551 polymorphism was related to ischemic stroke in Ukrainian population. The risk for this disease in patients with T/T genotype was higher than in major C-allele carriers (odds ratio (OR) = 3.117; 95% confidence interval (CI) = 1.016-9.566; Р = 0.047). After dividing patients into subgroups, formed by the presence of certain risk factors for atherosclerosis, similar association has been established for women and non-smokers. At the same time, the heterozygous genotype (C/T) in females had significantly protective effect against ischemic stroke development when compared to C/C and T/T genotypes (OR = 0.460; 95 % CI = 0.213-0.994; P = 0.048). Statistical significance of these results persisted even after adjustment for age, body mass index, smoking and hypertension.

Keywords: γ-glutamyl carboxylase; gene polymorphism; ischemic stroke.

References

  1. Soler EP, Ruiz VC. Epidemiology and Risk Factors of Cerebral Ischemia and Ischemic Heart Diseases: Similarities and Differences. Curr Cardiol Rev. 2010;6(3):138-49.
  2. CrossRef
  3. Margueritta S, Asmar E, Naoum J, Arbid E. Vitamin K Dependent Proteins and the Role of Vitamin K2 in the Modulation of Vascular Calcification: A Review. Oman Med J. 2014;29(3):172-7.
  4. CrossRef
  5. Pugliese G, Iacobini C, Fantauzzi CB, Menini S. The dark and bright side of atherosclerotic calcification. Atherosclerosis. 2015;238:220-30.
  6. CrossRef
  7. Stanford W. Coronary artery calcification as an indicator of preclinical coronary artery disease. Radiographics. 1999;19:1409-19.
  8. CrossRef
  9. Cortellaro M, Baldassarre D, Cofrancesco E, Tremoli E, Colombo A, Boschetti C, Paoletti R. Relation between hemostatic variables and increase of common carotid intima media thickness in patients with peripheral arterial disease. Stroke. 1996;27:450-4.
  10. doi: 10.1161/01. STR.27.3.450
  11. He M, Wen Z, He X, Xiong S, Liu F, Xu J, Li J, Xie Q, Jian Z, Chen F, Xiao B, Pu X, He S. Observation on tissue factor pathway and some other coagulation parameters during the onset of acute cerebrocardiac thrombotic diseases. Thromb Res. 2002;107(5):223-8.
  12. CrossRef
  13. Jood K, Ladenvall P, Tjärnlund-Wolf A, Ladenvall C, Andersson M, Nilsson S, Blomstrand C, Jern C. Fibrinolytic gene polymorphism and ischemic stroke. Stroke. 2005;36:2077-81.
  14. DOI: 10.1161/01. STR.0000183617.54752.69
  15. Viegas C, Rafael M, Enriquez J, Teixeira A, Vitorino R, Luís I, Costa R, Santos S, Cavaco S, Neves J, Macedo A, Willems B, Vermeer C, Simes D. Gla-rich protein acts as a calcification inhibitor in the human cardiovascular system. Arterioscler Thromb Vasc Biol. 2015;35(2):399- 408.
  16. CrossRef
  17. Laurance S, Lemarié C, Blostein M. Growth ArrestSpecific Gene 6 (gas6) and Vascular Hemostasis. Adv Nutr. 2012;3:196-203.
  18. CrossRef
  19. Oldenburg J, Marinova M, Muller-Reible C, Watzka M. The Vitamin K Cycle. Vitam Horm. 2008;78:35-62.
  20. CrossRef
  21. Watzka M, Geisen C, Scheer M, Wieland R, Wiegering V, Dörner T, Laws H, Gümrük F, Hanalioglu S, Ünal S, Albayrak D, Oldenburg J. Bleeding and nonbleeding phenotypes in patients with GGCX gene mutations. Thromb Res. 2014;134:856-65.
  22. CrossRef
  23. Adams HP, Bendixen BH, Kappelle LJ, Biller J, Love BB, Gordon DL, Marsh EE. Classification of subtype of acute ischemic stroke. Definitions for use in a multicenter clinical trial. TOAST. Trial of Org 10172 in Acute Stroke Treatment. Stroke. 1993;24:35-41.
  24. CrossRef
  25. Rieder MJ, Reiner AP, Rettie AE. γ-Glutamyl carboxylase (GGCX) tag SNPs have limited utility for predicting warfarin maintenance dose. J Thromb Haemost. 2007;5:2227-34.
  26. CrossRef
  27. Tie JK, Stafford DW. Structural and functional insights into enzymes of the vitamin K cycle. J Thromb Haemost. 2016;14:236-47.
  28. CrossRef
  29. Cha P, Mushiroda T, Takahashi A, Saito S, Shimomura H, Suzuki T, Kamatani N, Nakamura Y. High-resolution SNP and haplotype maps of the human gamma-glutamyl carboxylase gene (GGCX) and association study between polymorphisms in GGCX and the warfarin maintenance dose requirement of the Japanese population. Hum Genet. 2007;52:856-64.
  30. CrossRef
  31. Schelleman H, Brensinger C, Chen J, Finkelman B, Rieder M, Kimmel S. New genetic variant that might improve warfarin dose prediction in African Americans. Br J Clin Pharm. 2010;70(3):393-9.
  32. CrossRef
  33. Kamali X, Wulasihan M, Yang Y, Lu W, Liu Z, He P. Association of GGCX gene polymorphism with warfarin dose in atrial fibrillation population in Xinjiang. Lipids Health Dis. 2013;2(149):1-5.
  34. CrossRef
  35. Wu S, Cheung W, Frazier D, Stafford D. Cloning and Expression of the cDNA for Human y-Glutamyl Carboxylase. Science. 1991;254:1634-6.
  36. CrossRef
  37. Cavallari L, Perera M, Wadelius M, Deloukas P, Taube G, Patel S, Aquino-Michaels K, Viana A, Shapiro N, Nutescu E. Association of the GGCX (CAA)16/17 repeat polymorphism with higher warfarin dose requirements in African Americans. Pharmacogenet Genomics. 2012;22(2):152-8.
  38. CrossRef
  39. King C, Deych E, Milligan P, Eby C, Lenzini P, Grice G, Porche-Sorbet R, Ridker P, Gage B. Gamma-glutamyl carboxylase and its influence on warfarin dose. Thromb Haemost. 2010;104(4):750-4.
  40. CrossRef
  41. Wypasek E, Branicka A, Awsiuk M, Sadowski J, Undas A. Genetic determinants of acenocoumarol and warfarin maintenance dose requirements in Slavic population: A potential role of CYP4F2 and GGCX polymorphisms. Thromb Res. 2010;134:604-9.
  42. http://dx.doi.org/10.1016/j. thromres.2014.06.022
  43. Sun Y, Wub Z, Li S, Qin X, Li T, Xie L, Deng Y, Chen J. Impact of gamma-glutamyl carboxylase gene polymorphisms on warfarin dose requirement: A systematic review and meta-analysis. Thromb Res. 2015;135:739-47.
  44. CrossRef
  45. Tian L, Zhang J, Xiao S, Huang J, Zhang Y, Shen J. Impact of polymorphisms of the GGCX gene on maintenancewarfarin dose in Chinese populations: Systematic review and meta-analysis. Meta Gene. 2015;5:43-54.
  46. CrossRef
  47. Assimes T, Lee I, Juang J, Guo X, Wang T, Kim E, Lee W, Absher D, Chiu Y, Hsu C, Chuang L, Quertermous L, Hsiung C, Rotter J, Sheu W, Chen Y, Taylor K. Genetics of Coronary Artery Disease in Taiwan: A Cardiometabochip Study by the Taichi Consortium. PLoSOne. 2016;11(3):472- 9.
  48. doi:10.1371/journal. pone.0138014
  49. Ikejiri M, Wada H, Sakamoto Y, Ito N, Nishioka J, Nakatani K, Tsuji A, Yamada N, Nakamura N, Ito M, Nobori T. The association of protein S Tokushima-K196E with a risk of deep vein thrombosis. Int J Hematol. 2010;92:302- 5.
  50. CrossRef
  51. Visser M, Roshani S, Rutten J, Vlieg A, Vos H, Rosendaal F, Reitsma P. Haplotypes of VKORC1, NQO1 and GGCX, their effect on activity levels of vitamin K-dependent coagulation factors, and the risk of venous thrombosis. Thromb Haemost. 2011;106:563-5.
  52. CrossRef
  53. Shyu HY, Fong CS, Fu YP, Shieh JC, Yin JH, Chang CY, Wang HW, Cheng CW. Genotype polymorphisms of GGCX, NQO1, and VKORC1 genes associated with risk susceptibility in patients with large-artery atherosclerotic stroke. Clin Chim Acta. 2010;411:840-5.
  54. doi:10.1016/j. cca.2010.02.071
  55. Garbuzova VY, Stroy DA, Dosenko VE, Dubovyk YI, Borodenko AO, Shimko KA, Obukhova OA, Ataman OV. Association of allelic polymorphisms of genes matrix Gla-protein system with ischemic atherothrombotic stroke. Fiziol Zh. 2015;61(1):19-27. [Ukrainian].
  56. Ferron M, Lacombe J. Regulation of energy metabolism by the skeleton: osteocalcin and beyond. Arch Biochem Biophys. 2014;561:137-46.
  57. CrossRef
  58. Ferron M, Lacombe J, Germain A, Oury F, Karsenty G. GGCX and VKORC1 inhibit osteocalcin endocrine functions. J Cell Biol. 2015;208(6):761-76.
  59. doi/10.1083/jcb.201409111

© National Academy of Sciences of Ukraine, Bogomoletz Institute of Physiology, 2014-2019.