G2691A and C2491T mutations of factor V gene and pre-disposition to myocardial infarction in Morocco

Hmimech,Wiam; Diakite,Brehima; Idrissi,Hind  Hassani; Hamzi,Khalil; Korchi,Farah; Baghdadi,Dalila; Habbal,Rachida; Nadifi,Sellama

doi:10.3892/br.2016.768

G2691A and C2491T mutations of factor V gene and pre-disposition to myocardial infarction in Morocco

Authors:
- Wiam Hmimech
- Brehima Diakite
- Hind Hassani Idrissi
- Khalil Hamzi
- Farah Korchi
- Dalila Baghdadi
- Rachida Habbal
- Sellama Nadifi
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Affiliations: Laboratory of Genetics and Molecular Pathology, Medical School, University Hassan II, Casablanca 22000, Morocco, Department of Cardiology, University Hospital Center Ibn Rochd, Casablanca 22000, Morocco
Published online on: September 30, 2016 https://doi.org/10.3892/br.2016.768
Pages: 618-622

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Abstract

Coagulation factor Leiden mutation has been described as a common genetic risk factor for venous thrombosis; however, this mutation was reported to be practically absent in an African population. Recently, a novel non‑sense mutation in the gene encoding factor V has been associated with the risk of occurrence of cardio‑cerebrovascular diseases such as stroke and venous thrombosis. The aim of the present study was to investigate whether the factor V Leiden (FVL) and C2491T non‑sense mutations are associated with the risk of developing myocardial infarction. Genotyping of FVL and C2491T FV was performed using the polymerase chain reaction restriction fragment length polymorphism method on a sample of 100 patients with myocardial infarction as well as 211 controls. In the study population, the frequency of the FVL mutation was practically zero. However, with regard to the C2491T mutation, the TT genotype was associated with an increased risk of myocardial infarction [odds ratio (OR)=3.16, 95% confidence interval (CI): 1.29‑7.71, P=0.03]. A significant association between the C2491T FV mutation and the risk of myocardial infarction was identified using recessive (OR=2.74, 95% CI: 1.14‑6.58, P=0.04), dominant (OR=1.85, 95% CI: 1.13‑3.04, P=0.02) and additive (OR=1.88, 95% CI: 1.25‑2.80, P=0.004) models. Furthermore, a positive correlation was found between the presence of the C2491T FV mutation and hypertension (P=0.02), which is associated with myocardial infarction. In conclusion, the results of the present study suggested that the C2491T non-sense mutation of the FV gene may be a risk factor for myocardial infarction in a Moroccan population.

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1	Settin A, Dowaidar M, El-Baz R, Abd-Al-Samad A, El-Sayed I and Nasr M: Frequency of factor V Leiden mutation in Egyptian cases with myocardial infarction. Hematology. 13:170–174. 2008. View Article : Google Scholar : PubMed/NCBI
2	Zöller B and Dahlbäck B: Linkage between inherited resistance to activated protein C and factor V gene mutation in venous thrombosis. Lancet. 343:1536–1538. 1994. View Article : Google Scholar : PubMed/NCBI
3	Koster T, Rosendaal FR, de Ronde H, Briët E, Vandenbroucke JP and Bertina RM: Venous thrombosis due to poor anticoagulant response to activated protein C: Leiden Thrombophilia Study. Lancet. 342:1503–1506. 1993. View Article : Google Scholar : PubMed/NCBI
4	Hamzi K, Tazzite A and Nadifi S: Large-scale meta-analysis of genetic studies in ischemic stroke: Five genes involving 152,797 ndividuals. Indian J Hum Genet. 17:212–217. 2011. View Article : Google Scholar : PubMed/NCBI
5	Mannucci PM, Asselta R, Duga S, Guella I, Spreafico M, Lotta L, Merlini PA, Peyvandi F, Kathiresan S and Ardissino D: The association of factor V Leiden with myocardial infarction is replicated in 1880 patients with premature disease. J Thromb Haemost. 8:2116–2121. 2010. View Article : Google Scholar : PubMed/NCBI
6	Boekholdt SM, Bijsterveld NR, Moons AH, Levi M, Büller HR and Peters RJ: Genetic variation in coagulation and fibrinolytic proteins and their relation with acute myocardial infarction: A systematic review. Circulation. 104:3063–3068. 2001. View Article : Google Scholar : PubMed/NCBI
7	Ye Z, Liu EH, Higgins JP, Keavney BD, Lowe GD, Collins R and Danesh J: Seven haemostatic gene polymorphisms in coronary disease: Meta-analysis of 66,155 cases and 91,307 controls. Lancet. 367:651–658. 2006. View Article : Google Scholar : PubMed/NCBI
8	Kim RJ and Becker RC: Association between factor V Leiden, prothrombin G20210A, and methylenetetrahydrofolate reductase C677T mutations and events of the arterial circulatory system: A meta-analysis of published studies. Am Heart J. 146:948–957. 2003. View Article : Google Scholar : PubMed/NCBI
9	Juul K, Tybjaerg-Hansen A, Steffensen R, Kofoed S, Jensen G and Nordestgaard BG: Factor V Leiden: The Copenhagen City Heart Study and 2 meta-analyses. Blood. 100:3–10. 2002. View Article : Google Scholar : PubMed/NCBI
10	Lucotte G and Mercier G: Population genetics of factor V Leiden in Europe. Blood Cells Mol Dis. 27:362–367. 2001. View Article : Google Scholar : PubMed/NCBI
11	They-They TP, Hamzi K, Moutawafik MT, Bellayou H, El Messal M and Nadifi S: Prevalence of angiotensin-converting enzyme, methylenetetrahydrofolatereductase, Factor V Leiden, prothrombin and apolipoprotein E gene polymorphisms in Morocco. Ann Hum Biol. 37:767–77. 2010. View Article : Google Scholar : PubMed/NCBI
12	Mathonnet F, Nadifi S, Serazin-Leroy V, Dakouane M and Giudicelli Y: Absence of factor V Leiden mutation and low prothrombin G20210A mutation prevalence in a healthy Moroccan population. Thromb Haemost. 88:1073–1074. 2002.PubMed/NCBI
13	Rosing J and Tans G: Coagulation factor V: An old star shines again. Thromb Haemost. 78:427–433. 1997.PubMed/NCBI
14	van Wijk R, Nieuwenhuis K, van den Berg M, Huizinga EG, van der Meijden BB, Kraaijenhagen RJ and van Solinge WW: Five novel mutations in the gene for human blood coagulation factor V associated with type I factor V deficiency. Blood. 98:358–367. 2001. View Article : Google Scholar : PubMed/NCBI
15	Diakite B, Hamzi K, Hmimech W and Nadifi S: GMRAVC: First study of C2491T FV mutation with ischaemic stroke risk in Morocco. J Genet. 94:313–315. 2015. View Article : Google Scholar : PubMed/NCBI
16	Hamzi K, Diakité B, Hmimech W and Nadifi S: First study of the C2491t nonsense mutation frequency in moroccan healthy population. J Mol Neurosci. 51:425–427. 2013. View Article : Google Scholar : PubMed/NCBI
17	Dawson-Saunders B and Trapp RG: Basic and clinical biostatistics (2nd). Appleton and Lange. Norwalk, CT: 1994.
18	Miller SA, Dykes DD and Polesky HF: A simple salting out procedure for extracting DNA from human nucleated cells. Nucleic Acids Res. 16:12151988. View Article : Google Scholar : PubMed/NCBI
19	Huber S, McMaster KJ and Voelkerding KV: Analytical evaluation of primer engineered multiplex polymerase chain reaction-restriction fragment length polymorphism for detection of factor V Leiden and prothrombin G20210A. J Mol Diagn. 2:153–157. 2000. View Article : Google Scholar : PubMed/NCBI
20	Perneger TV: What's wrong with Bonferroni adjustments. BMJ. 316:1236–1238. 1998. View Article : Google Scholar : PubMed/NCBI
21	Delluc A, Le Ven F, Mottier D and Le Gal G: Epidemiology and risk factors of venous thromboembolism. Rev Mal Respir. 29:254–266. 2012.(In French). View Article : Google Scholar : PubMed/NCBI
22	Bertina RM: Molecular risk factors for thrombosis. Thromb Haemost. 82:601–609. 1999.PubMed/NCBI
23	Rosendaal FR: Risk factors for venous thrombotic disease. Thromb Haemost. 82:610–619. 1999.PubMed/NCBI
24	Sakowicz A, Fendler W, Lelonek M and Pietrucha T: Genetic variability and the risk of myocardial infarction in Poles under 45 years of age. Arch Med Sci. 6:160–167. 2010b. View Article : Google Scholar