Molecular Biology Reports

, Volume 41, Issue 3, pp 1779–1786 | Cite as

Matrix Gla protein (MGP) promoter polymorphic variants and its serum level in stenosis of coronary artery

  • Mohammad Najafi
  • Abazar Roustazadeh
  • Abdollah Amirfarhangi
  • Bahram Kazemi
Article

Abstract

Although the role of matrix Gla protein (MGP) is not completely known but, its expression within subendothelial macrophages and vascular smooth muscle cells is suggested to be involved in vascular calcification. In this study, we investigated the associations between the serum MGP levels and the MGP promoter high minor allele frequency (MAF) variants with the development of stenosis in coronary arteries. Moreover, we evaluated the allele changes within predicted transcription factor elements with bioinformatics tools. 182 subjects were recruited from who underwent coronary angiography. The MGP promoter rs1800801, rs1800802 and rs1800799 genotypes and haplotypes were detected by ARMS-RFLP PCR techniques. The serum MGP concentration was measured using ELISA method. Jaspar profiles were used for scoring the polymorphic variations within the transcription factor elements. The genotype and two-allelic haplotype distributions were not significant between the patient and control groups (P > 0.05). The serum MGP levels had not significant differences between the genotypes (P > 0.1) and haplotypes (P > 0.4). Based on the prediction studies, we did not observe significant differences between the polymorphic scores in the predicted elements (P > 0.05). We concluded that the genotype and haplotype distributions of the MGP promoter high-MAF polymorphisms, as confirmed in the prediction studies and the serum MGP level are not significantly associated with the coronary artery disease. Based on the study results, the MGP protein did not play an important role in the development of stenosis of coronary arteries.

Keywords

Matrix Gla protein Genotype Haplotype Prediction Coronary artery 

Supplementary material

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Supplementary material 1 (DOCX 13 kb)
11033_2014_3027_MOESM2_ESM.docx (13 kb)
Supplementary material 2 (DOCX 13 kb)
11033_2014_3027_MOESM3_ESM.docx (14 kb)
Supplementary material 3 (DOCX 13 kb)

References

  1. 1.
    Erbel R, Budoff M (2012) Improvement of cardiovascular risk prediction using coronary imaging: subclinical atherosclerosis: the memory of lifetime risk factor exposure. Eur Heart J 33:1201–1213PubMedCrossRefGoogle Scholar
  2. 2.
    Lee KB, Budoff MJ, Zavodni A, Polak JF, Jeffrey Carr J, Burke GL, Herrington DM (2012) Coronary artery calcium is associated with degree of stenosis and surface irregularity of carotid artery. Atherosclerosis 223:160–165PubMedCrossRefGoogle Scholar
  3. 3.
    Takeda Y, Hoshiga M, Tatsugami F, Morinaga I, Takehara K, Hotchi J, Yuki T, Ishihara T, Hanafusa T (2009) Clinical significance of calcification in ascending aorta as a marker for the requirement of coronary revascularization. J Atheroscler Thromb 16:346–354PubMedCrossRefGoogle Scholar
  4. 4.
    Brancaccio D, Biondi ML, Gallieni M, Turri O, Galassi A, Cecchini F, Russo D, Andreucci V, Cozzolino M (2005) Matrix GLA protein gene polymorphisms: clinical correlates and cardiovascular mortality in chronic kidney disease patients. Am J Nephrol 25:548–552PubMedCrossRefGoogle Scholar
  5. 5.
    Proudfoot D, Shanahan CM (2001) Biology of calcification in vascular cells: intima versus media. Herz 26:245–251PubMedCrossRefGoogle Scholar
  6. 6.
    Agatston AS, Janowitz WR, Hildner FJ, Zusmer NR, Viamonte MJ, Detrano R (1990) Quantification of coronary artery calcium using ultrafast computed tomography. J Am Coll Cardiol 15:827–832PubMedCrossRefGoogle Scholar
  7. 7.
    Schinke T, McKee MD, Krsenty G (1999) Extracellular matrix calcification: where is the action? Nat Genet 21:150–151PubMedCrossRefGoogle Scholar
  8. 8.
    Hackeng TM, Rosing J, Spronk HM, Vermeer C (2001) Total chemical synthesis of human matrix Gla protein. Protein Sci 10:864–870PubMedCrossRefGoogle Scholar
  9. 9.
    Doherty TM, Fitzpatrick LA, Inoue D, Qiao JH, Fishbein MC, Detrano RC, Shah PK, Rajavashisth TB (2004) Molecular, endocrine, and genetic mechanisms of arterial calcification. Endocr Rev 25:629–672PubMedCrossRefGoogle Scholar
  10. 10.
    Proudfoot D, Shanahan CM (2006) Molecular mechanisms mediating vascular calcification: role of matrix Gla protein. Nephrology (Carlton) 11:455–461CrossRefGoogle Scholar
  11. 11.
    Luo G, Ducy P, McKee MD, Pinero GJ, Loyer E, Behringer RR, Karsenty G (1997) Spontaneous calcification of arteries and cartilage in mice lacking matrix GLA protein. Nature 386:78–81PubMedCrossRefGoogle Scholar
  12. 12.
    Shanahan CM, Cary NR, Salisbury JR, Proudfoot D, Weissberg PL, Edmonds ME (1999) Medial localization of mineralization-regulating proteins in association with Monckeberg’s sclerosis: evidence for smooth muscle cell-mediated vascular calcification. Circulation 100:2168–2176PubMedCrossRefGoogle Scholar
  13. 13.
    Farzaneh-Far A, Davies JD, Braam LA, Spronk HM, Proudfoot D, Chan SW, O’Shaughnessy KM, Weissberg PL, Vermeer C, Shanahan CM (2001) A polymorphism of the human matrix gamma-carboxyglutamic acid protein promoter alters binding of an activating protein-1 complex and is associated with altered transcription and serum levels. J Biol Chem 276:32466–32473PubMedCrossRefGoogle Scholar
  14. 14.
    Herrmann SM, Whatling C, Brand E, Nicaud V, Gariepy J, Simon A, Evans A, Ruidavets JB, Arveiler D, Luc G, Tiret L, Henney A, Cambien F (2000) Polymorphisms of the human matrix gla protein (MGP) gene, vascular calcification, and myocardial infarction. Arterioscler Thromb Vasc Biol 20:2386–2393PubMedCrossRefGoogle Scholar
  15. 15.
    Munroe PB, Olgunturk RO, Fryns JP, Van Maldergem L, Ziereisen F, Yuksel B, Gardiner RM, Chung E (1999) Mutations in the gene encoding the human matrix Gla protein cause Keutel syndrome. Nat Genet 21:142–144PubMedCrossRefGoogle Scholar
  16. 16.
    Kobayashi N, Kitazawa R, Maeda S, Schurgers L, Kitazawa S (2004) T-138C polymorphism of matrix gla protein promoter alters its expression but is not directly associated with atherosclerotic vascular calcification. Kobe J Med Sci 50:69–81PubMedGoogle Scholar
  17. 17.
    Crosier MD, Booth SL, Peter I, Dawson-Hughes B, Price PA, O’Donnell CJ, Hoffmann U, Williamson MK, Ordovas JM (2009) Matrix Gla protein polymorphisms are associated with coronary artery calcification in men. J Nutr Sci Vitaminol (Tokyo) 55:59–65CrossRefGoogle Scholar
  18. 18.
    Adkins RM (2004) Comparison of the accuracy of methods of computational haplotype inference using a large empirical dataset. BMC Genet 3(5):22CrossRefGoogle Scholar
  19. 19.
    Roustazadeh A, Najafi M, Amirfarhangi A, Nourmohammadi I (2013) No association between MGP rs1800802 polymorphism and stenosis of the coronary artery. Ann Saudi Med 33:149–154PubMedGoogle Scholar
  20. 20.
    Frieldewald WT, Levy RI, Fredrickson DS (1972) Estimation of the concentration of low -density lipoprotein cholesterol in plasma, without use of the preparative ultracentifuge. Clin Chem 18:499–502Google Scholar
  21. 21.
    Miller SA, Dykes DD, Polesky HF (1988) A simple salting out procedure for extracting DNA from human nucleated cells. Nucleic Acids Res 16:1215PubMedCentralPubMedCrossRefGoogle Scholar
  22. 22.
    Najafi M, Gohari LH, Firoozrai M (2009) Paraoxonase 1 gene promoter polymorphisms are associated with the extent of stenosis in coronary arteries. Thromb Res 123:503–510PubMedCrossRefGoogle Scholar
  23. 23.
    Ataman AV, Garbusova VY, Ataman YA, Matlaj OI, Obuchova OA (2012) Investigation of the MGP promoter and exon 4 polymorphisms in patients with ischemic stroke in the Ukrainian population. J Cell Mol Biol 10:19–26Google Scholar
  24. 24.
    Harbuzova VIu, Hur’ianova VL, Parkhomenko OM, Dosenko VIe, Ataman OV (2011) The frequency of allelic polymorphism of matrix Gla-protein gene in acute coronary syndrome patients. Fiziol Zh 57:16–24PubMedGoogle Scholar
  25. 25.
    Jia G, Stormont RM, Gangahar DM, Agrawal DK (2012) Role of matrix Gla protein in angiotensin II-induced exacerbation of vascular stiffness. Am J Physiol Heart Circ Physiol 303:H523–H532PubMedCrossRefGoogle Scholar
  26. 26.
    Matsumoto K, Maniwa T, Tanaka T, Satoh K, Okunishi H, Oda T (2012) Proteomic analysis of calcified abdominal and thoracic aortic aneurysms. Int J Mol Med 30:417–429PubMedGoogle Scholar
  27. 27.
    Shea MK, O’Donnell CJ, Vermeer C, Magdeleyns EJ, Crosier MD, Gundberg CM, Ordovas JM, Kritchevsky SB, Booth SL (2011) Circulating uncarboxylated matrix gla protein is associated with vitamin K nutritional status, but not coronary artery calcium, in older adults. J Nutr 141:1529–1534PubMedCrossRefGoogle Scholar
  28. 28.
    Price PA, Faus SA, Williamson MK (1998) Warfarin causes rapid calcification of the elastic lamellae in rat arteries and heart valves. Arterioscler Thromb Vasc Biol 18:1400–1407PubMedCrossRefGoogle Scholar
  29. 29.
    Murshed M, Schinke T, McKee MD, Karsenty G (2004) Extracellular matrix mineralization is regulated locally; different roles of two gla-containing proteins. J Cell Biol 165:625–630PubMedCrossRefGoogle Scholar
  30. 30.
    Najafi M, Firoozrai M, Gohari HL, Zavarehie A, Basiri G (2007) Direct haplotyping of bi-allelic SNPs using Arms and RFLP analysis techniques. Biomol Eng 24:609–612PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media Dordrecht 2014

Authors and Affiliations

  • Mohammad Najafi
    • 1
  • Abazar Roustazadeh
    • 2
  • Abdollah Amirfarhangi
    • 3
  • Bahram Kazemi
    • 4
  1. 1.Biochemistry Department, Cellular and Molecular Research CenterIran University of Medical SciencesTehranIran
  2. 2.Jahrom University of Medical SciencesJahromIran
  3. 3.Hazrat-e Rasool HospitalIran University of Medical SciencesTehranIran
  4. 4.Shahid Beheshti University of Medical SciencesTehranIran

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