Association Between von Willebrand Factor (vWF) Gene Polymorphism and Coronary Heart Disease in Gaza Strip
American Journal of Life Sciences
Volume 4, Issue 2, April 2016, Pages: 51-59
Received: Apr. 14, 2016; Accepted: Apr. 25, 2016; Published: May 12, 2016
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Lamia'a Sobhi Saqer, Medical Sciences Department, University College of Science and Technology, Gaza Strip, Palestine
Mervat Jamal Kassab, Medical Sciences Department, University College of Science and Technology, Gaza Strip, Palestine
Ansam Khalid Alshehri, Medical Sciences Department, University College of Science and Technology, Gaza Strip, Palestine
Olfat M. Breaka, Medical Sciences Department, University College of Science and Technology, Gaza Strip, Palestine
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The von Willebrand Factor (vWF) gene located on Chromosome 12 spans ~ 180 kilobases with 52 exons. Changes in the vWF gene could alter VWF biosynthesis, secretion, clearance, and adhesion activity. Single nucleotide polymorphisms (SNPs) in exons, 5′ regulatory region, and introns are also reported to influence levels of vWF in healthy subjects. Some of these vWF SNPs are associated with an elevated risk for thrombosis and may be causally associated with coronary heart disease. The objective of this work was to detect the association between-1185A/G vWF gene polymorphism and CHD in Gaza strip. We conducted case-control study included 126 samples comprised 85 CHD patients and 41 control subjects. Questionnaire interview was applied. Blood samples were collected in EDTA tube for ABO blood grouping and DNA extraction. Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP) use to detect – 1185A/G polymorphism. The vWF -1185A/G genotype was the most common in the control and the CHD groups. The frequencies of vWF -1185 alleles in the CHD subjects were 0.541 for A and 0.459 for G. These frequencies are comparable to those found in the control group which were 0.622 for A and 0.378 for G. No statistically significant differences in vWF-1185 genotypes were found between the patients and the control groups. Moreover, there was no significant difference between the vWF-1185 polymorphism: gender, blood group, hypertension and diabetic in case and controls. However, there was a significant difference between the CHD: age, physical activity and education. To our knowledge, this is the first study in Gaza Strip investigating the relation between vWF-1185 A/G polymorphism and CHD. Further investigations are needed to link other genetic factors to CHD.
von Willebrand Factor Gene, Coronary Heart Disease, PCR-Restriction Fragment Length Polymorphism (PCR-RFLP)
To cite this article
Lamia'a Sobhi Saqer, Mervat Jamal Kassab, Ansam Khalid Alshehri, Olfat M. Breaka, Association Between von Willebrand Factor (vWF) Gene Polymorphism and Coronary Heart Disease in Gaza Strip, American Journal of Life Sciences. Vol. 4, No. 2, 2016, pp. 51-59. doi: 10.11648/j.ajls.20160402.16
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Z. Ruggeri, T. Zimmerman, “The complex multimeric composition of factor VIII/vWF”, Blood, pp 1140-1143, 1981.
J. Sadler, “Biochemistry and genetics of von Willebrand factor”, Annual Review of Biochemistry, 67, pp 395-424, 1998.
Z. Ruggeri, “Structure of von Willebrand factor and its function in platelet adhesion and thrombus formation”, Best Practice & Research Clinical Haematology, pp 257-259, 2001.
G. Lowe, “Haemostatic risk factors for arterial and venous thrombosis in: Poller L, Ludlam CA (ed ”, Recent advances in blood coagulation Edinburgh, Churchill Livingstone, pp 69-96, 1997.
D. Mancuso, E. Tuley, L. Westfield, N. Worrall, B. Shelton-Inloes, J. Sorace, Y. Alevy, J. Sadler, “Structure of the gene for human von Willebrand factor”, Journal of Biological Chemistry, pp 19514-19527, 1989.
T. Canciani, A. Federici, “Clinical and laboratory versus molecular markers for a correct classification of von Willebrand disease”, haematologica, 94 (5), pp 610-615.
P. James, D. Lillicrap, “Genetic testing for von Willebrand disease: the Canadian experience”, Seminars in Thrombosis and Hemostasis, 32, pp 546-552, 2006.
P. Casana, F. Martinez, S. Haya, A. Tavares, J. Aznar, “New mutations in exon 28 of the von Willebrand factor gene detected in patients with different types of von Willebrand's disease”, Haematologica, 86, pp 414-419, 2001.
E. Bladbjerg, M. de Maat, Christensen K, Bathum L, J. Jespersen, J. Hjelmborg, “Genetic influence on thrombotic risk markers in the elderly”, Journal Thrombosis Haemostsis, 4 (3), pp 599-607, 2006.
M. Lange, H. Snieder, R. Ariens, T. Spector, P. Grant, “The genetics of haemostasis”, Lancet, 357 (9250), pp 101-105, 2001.
J. Souto, L. Almasy, M. Borrell, “Genetic susceptibility to thrombosis and its relationship to physiological risk factors. Genetic analysis of idiopathic thrombophilia”, American Journal Human Genetics, pp 1452-1459, 2000.
T. Larsen, H. Sorensen, A. Skytthe, S. Johnsen, J. Vaupel, K. Christensen, “Major genetic susceptibility for venous thromboembolism in men”, Epidemiology, pp 328-332, 2003.
J. O'Donnell, M. Lasffan, “The relationship between ABO histo blood group, factor VIII and von Willebrand factor”, Transfusion Medicine, pp 343-351, 2001.
P. Jenkins, J. O'Donnell, “ABO blood group determines plasma von Willebrand factor levels: a biologic function after all?, Transfusion, pp 1836-1844, 2006.
A. Fosang, P. Smith, “To clot or not”, Nature, pp 475–481, 2001.
R. Bitondo, C. Cameron, M. Daly, S. Croft, R. Steeds, K. Channer, N. Samani, D. Lillicrap and P. Winship, “The 21185 A/G and 21051 G/A dimorphisms in the von Willebrand factor gene promoter and risk of myocardial Infarction”, British Journal of Haematology, 115, pp 701-706, 2001.
J. Gersh, S. Karen, M. Bongani and Y. Salim, “The epidemic of cardiovascular disease in the developing world global implications”, European Heart Journal, 31 (6), pp 642-650, 2010.
S. Khwaiter, “Risk factors associated with coronary artery disease in Gaza”, MSC thesis, IUG of Gaza, Palestine, 2009.
M. Mushtaha, “Risk factors of in coronary artery disease patients undergoing cardiac catheterization in Gaza governorates”, British Journal of Medicine & Medical Research, 5 (1), pp 88-97, 2010.
W. Castelli, “Epidemiology of coronary heart disease: the Framingham B Study”, American Journal of Medicine, 76, pp 4–12, 1984.
R. Jackson, L. Chambless, M. Higgins, K. Kuulasmaa, L. Wijnberg, D. Williams, “Sex difference in ischaemic heart disease mortality and risk factors in 46 communities: an ecologic analysis”, Cardiovasc Risk Factors, 7, pp 43–54, 1997.
M. Izadnegahdar, J. Singer, M. Lee, M. Gao, C. Thompson, J. Kopec, “Do younger women fare worse? Sex differences in acute myocardial infarction hospitalization and early mortality rates over ten years”, Journal of Womens Health, 23 (1), pp 10-17, 2014.
F. Sozzi, G.. Danzi, L. Foco, M. Ferlini, M. Tubaro, M. Galli, “Myocardial infarction in the young: a sex-based comparison”, coronary artery disease, 18 (6), pp 429–431, 2007.
K. Matthews, E. Meilahn, L. Kuller, S. Kelsey, A. Caggiula, R. Wing, “Menopause and risk factors for coronary heart disease”, New England Journal of Medicine, 321, pp 641–646, 1989.
C. Bonithon-Kopp, P. Scarabin, B. Darne, A. Malmejak, L. Guize, “Menopause-related changes in lipoproteins and some other cardiovascular risk factors”, International Journal of Epidemiology, 19, pp 42–48, 1990.
D. Grady, S. Rubin, D. Petitti, C. Fox, D. Black, B. Ettinger, V. Ernster, S. Cummings, “Hormone therapy to prevent disease and prolong life in postmenopausal women”, Annals of Internal Medicine, 117, pp. 1016–1037, 1992.
E. Shahar, A. Folsom, V. Salomaa, V. Stinson, P. McGovern, T. Shimakawa, L. Chambless, K. Wu, “For the atherosclerosis risk in communities (ARIC) study investigators. relation of hormone replacement therapy to measures of plasma fibrinolytic activity”, Circulation, 93, pp 1970 –1975, 1996.
V. Perova, E. Davis, S. Tao, A. Pajak, Y. Stein, G. Broda, H. Tyroler, “Multi-country comparison of plasma lipid relationship to years of schooling in men and women”, International Journal of Epidemiology, 30, pp 371-379, 2001.
V. Press, I. Freestone, C. George, “Physical activity: the evidence of benefit in the prevention of coronary heart disease”, Quarterly journal of medicine, 96, pp 245–251, 2003.
C. Bouchard, “Physical activity and prevention of cardiovascular diseases: potential mechanisms. physical activity and cardiovascular health”, Champaign IL, Human Kinetics, pp 48–56, 1997.
G. Kaplan, J. Keil, “Socioeconomic factors and cardiovascular disease: a review of literature”, Circulation, 88, pp 1973-1998, 1993.
C. Lenfant, “Conference on socioeconomic status and cardiovascular health and disease”, Circulation, 94, pp 2041-2044, 1996.
S. Wamala, K. Orth-Gomer, “Interfaces of human biology and social organization: challenges for future research. In: Inequality in Health-A Swedish perspective: contributions from Swedish researchers in the social, behavioral and medical sciences for a national research program on inequality in health”, Swedish Social Research Council, pp 113-130, 1998.
M. Albert, R. Glynn, J. Buring, P. Ridker, “Impact of traditional and novel risk factors on the relationship between socioeconomic status and incident cardiovascular events”, Circulation, 12, pp 2619–2645, 2006.
E. Loucks, J. Lynch, L. Pilote, R. Fuhrer, N. Almeida, H. Richard, G. Agha, J. Murabito, E. Benjamin, “Life-course socioeconomic position and incidence of coronary heart disease. The Framingham offspring study”, American Journal of Epidemiology, 169 (7), pp 829-836, 2009.
K. Giskes, M. Avendano, J. Brug, A. Kunst, “A systematic review of studies on socioeconomic inequalities in dietary intakes associated with weight gain and overweight/obesity conducted among European adults”, Obesity reviews, 11 (6), pp 413–429, 2010.
S. Gilman, L. Martin, D. Abrams, I. Kawachi, L. Kubzansky, E. Loucks, R. Rende, R. Rudd, S. Buka, “Educational attainment and cigarette smoking: a causal association”, International Journal of Epidemiology, 37 (3), pp 615–624, 2008.
O. Wu, N. Bayoumi, M. Vickers, P. Clark, “ABO (H) blood groups and vascular disease: asystematic review and meta‑analysis”, Journal of Thrombosis and Haemostasis, 6, pp 62-69, 2008.
F. Dentali, A. Sironi, W. Ageno, C. Bonfanti, S. Crestani, F. Frattini, L. Steidl, M. Franchini, “Relationship between ABO blood group and hemorrhage: a systematic literature review and meta-analysis”, Semin Thromb Hemost, 39, pp 72–82, 2013.
A. Keightley, Y. Lam, J. Brady, C. Cameron, D. Lillicrap, “Variation at the von Willebrand factor (VWF) gene locus is associated with plasma VWF: Ag levels: identification of three novel single nucleotide polymorphisms in the VWF gene promoter”, Blood, 93, pp 4277-4283, 1999.
P. Harvey, A. Keightley, Y. Lam, C. Cameron, D. Lillicrap, “A single nucleotide polymorphism at nucleotide -1793 in the von Willebrand factor (VWF) regulatory region is associated with plasma VWF: Ag levels”, British Journal of Haematology, 109, pp 349-353, 2000.
Z. Zhang, M. Blombäck, N. Egberg, G. Falk, M. Anvret, “Characterization of the von Willebrand factor gene (VWF) in von Willebrand disease type III patients from 24 families of Swedish and Finnish origin”, Genomics, 21, pp 188-193, 1994.
P. Kamphuisen, J. Eikenboom, F. Rosendaal, T. Koster, A. Blann, H. Vos, R. Bertina, “High factor VIII antigen levels increase the risk of venous thrombosis but are not associated with polymorphisms in the von Willebrand factor and factor VIII gene”, British Journal of Haematology, 115, pp 156-158, 2001.
K. Tompkins, C. Cameron, J. Brady, S. Raj, A. Keightley, D. Lillicrap, “Polymorphisms in the glycoprotein Ibα, α2 integrin and von Willebrand factor genes: possible implications in platelet adhesion and acute coronary events”, Blood, 94-165, 1999.
R. Di Bitondo, C. Cameron, M. Daly, S. Croft, R. Steeds, K. Channer, N. Samani, D. Lillicrap, P. Winship, “The -1185 A/G and -1051 G/A dimorphisms in the von Willebrand factor gene promoter and risk of myocardial infarction”, British Journal of Haematology, 115, pp 701-706, 2001.
A. Preston, A. Barr, “The plasma concentration of factor VIII in the normal population”, British Journal of Haematology, 10, pp 238-283, 1964.
J. Gill, J. Endres-Brooks, P. Bauer, W. Marks, R. Montgomery, “The effect of ABO blood group on the diagnosis of von Willebrand disease”, Blood, 69, pp 1691-1696, 1987.
T. Matsui, K. Titani, T. Mizuochi, “Structures of the asparagine linked oligosaccharide chains of human von Willebrand factor Occurrence of blood group A, B, and H (O) structures”, Journal of Biological Chemistry, 267, pp 8723-8731, 1992.
J. Sodetz, S. Pizzo, P. McKee, “Relationship of sialic acid to function and in vivo survival of human factor VIII/von Willebrand factor protein”, Journal of Biological Chemistry, 252, pp 5538-46, 1977.
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