Leyla AYDOĞAN, Şemsettin ŞAHİN, İsmail BENLİ

Distribution of prothrombin G20210A, factor V Leiden, and MTHFR C677T mutations in the middle Black Sea area (Tokat) of Turkey

To determine the distribution frequencies of prothrombin (factor II) G20210A, factor V Leiden, and methylenetetrahydrofolate reductase (MTHFR) C677T mutations in Tokat Province and the middle Black Sea area of Turkey. Materials and methods: The study group consisted of 243 patients who presented to our center with thrombosis and other complaints. Written permission from patients was obtained. DNA was isolated from the blood samples of these patients. Mutation analyses were conducted using the real-time polymerase chain reaction (RT-PCR) method. The data were subjected to statistical analyses. Results: According to the results of the study, factor V Leiden was detected in 37 patients, prothrombin G20210A was detected in 5 patients, and MTHFR C677T was detected in 146 patients. On the other hand, 79 patients carried none of these mutations. Conclusion: Factor V Leiden mutation was detected at a rate of 15.2%, which is much higher than the average in Turkey. The G20210A mutation rate in the prothrombin gene was determined as 2.1%. The MTHFR C677T mutation incidence was quite high (60%). The homozygous mutation rate was higher in diagnoses involving thrombosis, while the heterozygous mutation rate was higher in other diagnoses.

Anahtar Kelimeler:

Key words: Thrombosis, factor V Leiden, prothrombin, G20210A, MTHFR, C677T

Distribution of prothrombin G20210A, factor V Leiden, and MTHFR C677T mutations in the middle Black Sea area (Tokat) of Turkey

Keywords:

Key words: Thrombosis, factor V Leiden, prothrombin, G20210A, MTHFR, C677T,

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Gürgey A, Özyürek EH. Tromboza neden olan herediter faktörler. Katkı Pediatri Dergisi 2001; 22: 170-7 (in Turkish). 2. Lanzkowsky P. Manual of pediatric hematology and oncology. 3rd ed. San Diego (CA): Academic Press; 2000. p.233-87.
Ulutin O. Ulusal Tromboz, Hemostaz ve Anjioloji Kongresi kitabı. İstanbul: May Matbaacılık Ltd.; 2001 (in Turkish).
Goodnight SH, Griffi n JH. Hereditary thrombophilia. In: Beutler E, Lichtman MA, Coller BS, Kipps TJ, Seligsohn U, editors. Williams hematology. 6th ed. New York: McGraw-Hill; 2001. p.1551-81.
Carp H, Salomon O, Seidman D, Dardik R, Rosenberg N, Inbal A. Prevalence of genetic markers for thrombophilia in recurrent pregnancy loss. Hum Reprod 2002; 17: 1633-7.
Bick RL, Hoppensteadt D. Recurrent miscarriage syndrome and infertility due to blood coagulation protein/platelet defects: a review and update. Clin Appl Th romb Hemost 2005; 11: 1-13.
Foka ZJ, Lambropo ulos AF, Saravelos H, Karas GB, Karavida A, Agorastos T et al. Factor V Leiden and prothrombin G20210A mutations, but not methylenetetrahydrofolate reductase C677T, are associated with recurrent miscarriages. Hum Reprod 2000; 15: 458-62. 8. Pauer HU, Voig-Ts chitschwitz T, Hinney B, Burfeind F, Wolf C, Emons G et al. Analysis of three common thrombophilic gene mutations in German women with recurrent abortions. Acta Obstet Gynecol Scand 2003; 82: 942-7.
Bertina RM, Koeleman BP, Koster T, Rosendaal FR, Dirven RJ, de Ronde H et al. Mutation in blood coagulation factor V associated with resistance to activated protein C. Nature 1994; 369: 64-7.
Heeb MJ, Kojima Y, Greengard JS, Griffi n JH. Activated protein C resistance: molecular mechanisms based on studies using purifi ed Gln506-factor V. Blood 1995; 85: 3405-11.
Franchini M, Manucci PM. Multiple gene interaction and modulation of hemostatic balance. Clin Chem Lab Med 2009; 47: 1455-60.
Lindqvist PG, Dahlbäck B, Carriership of factor V Leiden and evolutionary selection advantage. Curr Med Chem 2008; 15: 1541-4.
Nguyen A. Prothrombin G20210A polymorphism and thrombophilia. Mayo Clin Proc 2000; 75: 595-604.
Poort SR, Rosendaal FR , Reitsma PH, Bertina RM. A common genetic variation in the 3’-untranslated region of the prothrombin gene is associated with elevated plasma prothrombin levels and an increase in venous thrombosis. Blood 1996; 88: 3698-703.
Th ey-Th ey TP, Battas O, Slassi I, Rafai MA, Katumbay DT, Nadifi S. Prothrombin G20210A and factor V Leiden polymorphisms in stroke. J Mol Neurosci 2012; 46: 210-6.
Wouters MG, Boers G H, Blom HJ, Trijbels FJ, Th omas CM, Borm GF et al. Hyperhomocysteinemia: a risk factor in women with unexplained recurrent early pregnancy loss. Fertil Steril 1993; 60: 820-5.
Bhagwat VR, Yadav AS, Rathod IM. Homocysteine, lipid indices and antioxidants in patients with ischaemic heart disease from Maharashtra, India. Singapore Med J 2009; 50: 418-24.
Reitsma PH. Genetic heterogeneity in hereditary thrombophilia. Haemostasis 2000; 30 Suppl 2: 1-10.
Lee R. Factor V Leiden: a clinical review. Am J Med Sci 2001; 322: 88-102.
Rosenberg RD. Vascular-bed-specifi c hemostasis and
hypercoagulable states: clinical utility of activation peptide
assays in predicting thrombotic events in diff erent clinical
populations. Th romb Haemost 2001; 86: 41-50.
Dahlbäck B. Advances in understanding pathogenic mechanisms of thrombophilic disorders. Blood 2008; 112: 19- 27.
Akar N, Akar E, Dalgın G, Sözüöz A, Ömürlü K, Cin S. Frequency of Factor V (1691 G-A) mutation in Turkish population. Th romb Haemost 1997; 78: 1527-8.
Makris M. Th rombophilia: grading the risk. Blood 2009; 113: 5038-9.
Rosendaal FR, Doggen CJ, Zivelin A, Arruda VR, Aiach M, Siscovick DS et al. Geographic distribution of the 20210 G to A prothrombin variant. Th romb Haemost 1998; 79: 706-8.
Th omas P, Fenech M. Methylenetetrahydrofolate reductase, common polymorphisms, and relation to disease. Vitam Horm 2008; 79: 375-92.
Homberger G, Linnebank M, Winter C, Willenbring H, Marquardt T, Harms E et al. Genomic structure and transcript variants of the human methylenetetrahydrofolate reductase gene. Eur J Hum Genet 2000; 8: 725-9.
Rady PL, Tyring SK, Hudnall SD, Vargas T, Kellner LH, Nitowsky H et al. Methylenetetrahydrofolate reductase (MTHFR): the incidence of mutations C677T and A1298C in the Ashkenazi Jewish population. Am J Med Genet 1999; 86: 380-4.
Sazci A, Ergul E, Kaya G, K ara I. Genotype and allele frequencies of the polymorphic methylenetetrahydrofolate reductase gene in Turkey. Cell Biochem Funct 2005; 23: 51-4.