AIM: The aim was to analyze association of Factor V Leiden (G1691A), Factor V R2 (A4070G), and Prothrombin (G20210A) Genetic Polymorphism in Macedonian Patients with Occlusive Artery Disease (OAD) and Deep Vein Thrombosis (DVT).
METHODS: Investigated groups consists of 82 healthy, 76 patients with OAD, and 67 patients with DVT. Blood samples were collected after written consent, and DNA was isolated from peripheral blood leukocytes. Identification of Factor V Leiden (G1691A), Factor V R2 (A4070G), and Prothrombin (G20210A) Genetic Polymorphism was done with CVD StripAssay (ViennaLab, Labordiagnostica GmbH, Austria). The population genetics analysis package, PyPop, was used for analysis of the data. Pearson's P-values, crude Odds Ratio and Wald's 95% CI were calculated.
RESULTS: The frequency of G allele for Factor V Leiden was 0.976 for healthy participants, 0.954 for OAD, and 0.948 for DVT. The frequency of A allele for Factor R2 is highest in healthy participants (0.951), smaller in patients with DVT (0.918), and smallest in the patients with OAD (0.908). G allele frequency for prothrombin was 0.976 in healthy participants, 0.980 in patients with OAD, and 0.978 in patients with DVT. Test of neutrality (Fnd) showed positive value, but was not significantly different from 0. Factor V Leiden (G1691A), Factor R2 (A4070G), and Prothrombin (G20210A) genotypes in healthy participants and patients with OAD and DVT were in Hardy Weinberg proportions. Any association of Factor V Leiden (G1691A), Factor R2 (A4070G), and Prothrombin (G20210A) genetic polymorphism with OAD, and DVT in Macedonians was not found.CONCLUSION: We conclude that significant association of Factor V Leiden (G1691A), Factor R2 (A4070G), and Prothrombin (G20210A) genetic polymorphism with occlusive artery disease or deep venous thrombosis in Macedonians was not found.
Kim RJ, 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. 2003;146(6):948-57.
Ye Z, Liu EH, Higgins JP, Keavney BD, Lowe GD, Collins R, Danesh J. Seven haemostatic gene polymorphisms in coronary disease: meta-analysis of 66,155 cases and 91,307 controls. Lancet. 2006;367(9511):651-8.
Keijzer MB, Borm GF, Blom HJ, Bos GM, Rosendaal FR, den Heijer M. No interaction between factor V Leiden and hyperhomocysteinemia or MTHFR 677TT genotype in venous thrombosis. Results of a meta-analysis of published studies and a large case-only study. Thromb Haemost. 2007;97(1):32-7.
Gohil R, Peck G, Sharma P. The genetics of venous thromboembolism. A meta-analysis involving approximately 120,000 cases and 180,000 controls. Thromb Haemost. 2009;102(2):360-70.
Marjot T, Yadav S, Hasan N, Bentley P, Sharma P. Genes associated with adult cerebral venous thrombosis. Stroke. 2011;42(4):913-8.
Spiroski I, Kedev S, Antov S, Arsov T, Krstevska M, Dzhekova-Stojkova S, Kostovska S, Trajkov D, Petlichkovski A, Strezova A, Efinska-Mladenovska O, Spiroski M. Association of methylenetetrahydrofolate reductase (MTHFR-677 and MTHFR-1298) genetic polymorphisms with occlusive artery disease and deep venous thrombosis in Macedonians. Croat Med J. 2008;49(1):39-49.
Spiroski I, Kedev S, Antov S, Arsov T, Krstevska M, Dzhekova-Stojkova S, Bosilkova G, Kostovska S, Trajkov D, Petlichkovski A, Strezova A, Efinska-Mladenovska O, Spiroski M. Methylenetetrahydrofolate reductase (MTHFR-677 and MTHFR-1298) genotypes and haplotypes and plasma homocysteine levels in patients with occlusive artery disease and deep venous thrombosis. Acta Biochim Pol. 2008;55(3):587-94.
Spiroski I, Kedev S, Antov S, Trajkov D, Petlichkovski A, Dzhekova-Stojkova S, Kostovska S, Spiroski M. Investigation of SERPINE1 genetic polymorphism in Macedonian patients with occlusive artery disease and deep vein thrombosis. Kardiol Pol. 2009;67(10):1088-1094.
Towner P. Purification of DNA. Essential Molecular Biology (ed.T.A.Brown). Oxford University Press, Oxford. 1995:47-54.
Spiroski M, Arsov T, Petlichkovski A, Strezova A, Trajkov D, Efinska-Mladenovska O, et al. Case Study: Macedonian Human DNA Bank (hDNAMKD) as a source for public health Genetics. In: Health Determinants in the Scope of New Public Health. Ed. by Georgieva L, Burazeri G. Hans Jacobs Company: Sofia, 2005:33-44.
Mahfouz RA, Sabbagh AS, Shammaa DM, Otrock ZK, Zaatari GS, Taher AT. Factor XIII gene V34L mutation in the Lebanese population: Another unique feature in this community? Mol Biol Rep. 2008;35(3):375-8.
Lancaster A, Nelson MP, Meyer D, Thomson G, Single RM. PyPop: a software framework for population genomics: analyzing large-scale multi-locus genotype data. Pac Symp Biocomput. 2003;514-25.
Lancaster AK, Single RM, Solberg OD, Nelson MP, Thomson G. PyPop update--a software pipeline for large-scale multilocus population genomics. Tissue Antigens. 2007;69(Suppl 1):192-7.
Single RM, Meyer D, Mack SJ, Lancaster A, Erlich HA, Thomson G. 14th International HLA and Immunogenetics Workshop: report of progress in methodology, data collection, and analyses. Tissue Antigens. 2007;69(Suppl 1):185-7.
Guo S, Thomson E. Performing the exact test of Hardy Weinberg proportion for multiple alleles. Biometrics. 1992;48:361.
Schneider S, Roessli D, Excoffier L. Arlequin version 2.000: a software for population genetics data analysis. Geneva (Switzerland): Genetics and Biometry Laboratory, University of Geneva; 2000.
Watterson GA. The homozygozity test of neutrality. Genetics. 1978; 88: 405-17.
Slatkin M, Excoffier L. Testing for linkage disequilibrium in genotypic data using the Expectation-Maximization algorithm. Heredity. 1996;76(Pt 4):377-83.
Slatkin M. An exact test for neutrality based on the Ewens sampling distribution. Genet Res. 1994;64:71-4.
Rice TK, Schork NJ, Rao DC. Methods for handling multiple testing. Adv Genet. 2008;60:293-308.
Holm S. A simple sequentially rejective Bonferroni test procedure. Scand J Statist. 1979;6:65 -70.
Pare G, Serre D, Brisson D, Anand SS, Montpetit A, Tremblay G, et al. Genetic analysis of 103 candidate genes for coronary artery disease and associated phenotypes in a founder population reveals a new association between endothelin-1 and high-density lipoprotein cholesterol. Am J Hum Genet. 2007;80(4):673-82.
van Stralen KJ, Doggen CJ, Bezemer ID, Pomp ER, Lisman T, Rosendaal FR. Mechanisms of the factor V Leiden paradox. Arterioscler Thromb Vasc Biol. 2008;28(10):1872-7.