Printer Friendly

Factor V 1691 G-A mutation distribution in a healthy Turkish population/Saglikli Turk populasyonunda faktor V (1691 G-A) mutasyon sikligi.

Factor V Leiden (1691 G-A) (FVL) causes activated protein C resistance and is the most common thrombophilic mutation worldwide. Guanine to adenine change leads to a replacement of glutamine to arginine at amino acid position 506. It is most prevalent among Caucasians but not found in Japanese and Africans [1,2].

Anatolia is at the crossroads of different civilizations and lies central to three continents. Thus, it is logical that different frequencies could be expected in different parts of the country. However, as FVL is presumed to have originated from the Middle East some 15,000-30,000 years ago, high frequency among the Turkish population can be expected [3].

The data in this review was compiled from PubMed and Science Citation Index databases. "Factor V Leiden, Factor V 1691 G-A, FVL" were used as key words and cross-searched with the key words "Turkish population and Turkey". The first publication from each center was included in the study. Published studies with their geographical region, number of controls, number of individuals carrying FVL and references are given in Table 1. Two studies from Ankara and Bursa were performed among newborns and are shown in Table 2.

FVL frequency in the Turkish population has been reported from different parts of Turkey. Frequency was reported to range between 3.5 to 15% in several studies [4-29]. This wide range may be explained by either the small sample size of the studies or by geographical location of the previous studies. However, it is interesting that when all the published controls were summed, a frequency of 7.9% of carriers was found (4276 individuals with 345 FVL heterozygous carriers). Ankara and Istanbul are metropolitan cities and given the composition of their populations, both cities represent a good example for screening studies of the Turkish population. When the published related studies were reviewed, FVL frequency was determined as 7.5% in Ankara and 8.3% in Istanbul. These two values are almost identical to the sum of all published controls for FVL frequency.

It is interesting to find FVL strikingly high among newborns from two different centers, i.e. Ankara and Bursa [30,31]. Although there are only two reports, a marked difference between adult and newborn frequency may have importance (7.9% vs 10.9%). This calls to mind the question, "Did some of the infants with FVL mutation die of clinical conditions related with thromboembolism before reaching adult age and without receiving a specific diagnosis?" This may explain the difference between the frequencies in newborns and adults [30,32]. Although the difference was not statistically significant in our data (p: 0.06), if this hypothesis is verified by other studies, it will be a very important finding from an evolutionary point of view.

FV 1691 G-A mutation was found to be 12.2% in Turkish Cypriots [5]. Previous studies revealed the allele frequency to be 8.0% in Greek Cypriots [33]. Thus, it can be said that the prevalence of this particular mutation is very high in Turkish Cypriots, almost similar to that of thalassemia syndromes, which are the commonest genetic disease in Cyprus. As Cyprus is an island, finding a high frequency of FVL seems logical [34]. The difference between the two communities may be explained by the first Turkish immigration in 1570 from middle Anatolia, and then again in 1974. Further, it is well known that while Muslim men marry Christian women, it is very rare for Muslim women to marry Christian men. With these two mentioned points, the different incidence between the two populations, although they co-exist on the same island, can be expected.

In conclusion, this review was undertaken in order to compile the previously reported data and also to stimulate the reporting of unpublished data, in order to create a map for FVL in Turkey.

Received: January 14, 2008 Accepted: September 10, 2008

Gelis tarihi: 14 Ocak 2008 Kabul tarihi: 10 Eylul 2008


[1.] Rees DC, Cox M, Clegg JB. World distribution of factor V Leiden. Lancet 1995;346:1133-4.

[2.] Bertina RM, Koeleman BP, Koster T, Rosendaal FR, Dirven RJ, de Ronde H, van der Velden PA, Reitsma PH. Mutation in blood coagulation factor V associated with resistance to activated protein C. Nature 1994;369:64-7.

[3.] Pawar AR, Shetty S, Ghosh K, Mohanty D. How old is factor V Leiden mutation? Thromb Haemost 2001;86:1591-2.

[4.] Donmez Y, Kanadasi M, Tanriverdi K, Demir M, Demirtas M, Cayli M, Alhan C, Baslamisli F Prothrombin 20210GA and factor V Leiden mutations in patients less than 55 years old with myocardial infarction. Jpn Heart J 2004;45:505-12.

[5.] Akar N, Akar E, Dalgin G, Sozuoz A, Omurlu K, Cin S. Frequency of factor V (1691 G --> A) mutation in Turkish population. Thromb Haemost 1997;78:1527-8.

[6.] Gurgey A, Mesci L. The prevalence of factor V Leiden (1691 G-->A) mutation in Turkey. Turk J Pediatr 1997;39:313-5.

[7.] Aras S, Yilmaz G, Alpas I, Baltaci V, Tayanc E, Aydin P Retinal vein occlusion and factor V Leiden and prothrombin 20210 G:A mutations. EurJ Ophthalmol2001;11:351-5.

[8.] Erkan O, Bozdayi AM, Disibeyaz S, Oguz D, Ozcan M, Bahar K, Karayalcin S, Ozden A, Bozkaya H, Yurdaydin C, Uzunalimoglu O. Thrombophilic gene mutations in cirrhotic patients with portal vein thrombosis. Eur J Gastroenterol Hepatol 2005;17:339-43.

[9.] Toydemir PB, Elhan AH, Tukun A, Toydemir R, Gurler A, Tuzuner A, Bokesoy I. Effects of factor V gene G1 691A, methylenetetrahydrofolate reductase gene C677T, and prothrombin gene G2021 OA mutations on deep venous thrombogenesis in Beh9et's disease. J Rheumatol 2000;27:2849-54.

[10.] Yasa MH, Bolaman Z, Yukselen V, Kadikoylu G, Karaoglul AO, Batun S. Factor V Leiden G1 691 A, prothrombin G2021 OA, and MTHFR C677T mutations in Turkish inflammatory bowel disease patients. Hepatogastroenterology 2007;54:1438-42.

[11.] Agaoglu N, Turkyilmaz S, Ovali E, Ucar F, Agaoglu C. Prevalence of prothrombotic abnormalities in patients with acute mesenteric ischemia. World J Surg 2005;29:1135-8.

[12.] Kabukcu S, Keskin N, Keskin A, Atalay E. The frequency of factor V Leiden and concomitance of factor V Leiden with prothrombin G2021 OA mutation in healthy population of Denizli, Aegan region of Turkey. Clin Appl Thromb Hemost 2007;13:166-71.

[13.] Irdem A, Devecioglu C, Batun S, Soker M, Sucakli IA. Prevalence of factor V Leiden and prothrombin G20210A gene mutation. Saudi Med J 2005;26:580-3.

[14.] Yilmaz S, Bayan K, Tuzun Y, Batun S, Altintas A. A comprehensive analysis of 12 thromboembolic mutations and related parameters in patients with inflammatory bowel disease: data from Turkey. J Thromb Thrombolysis 2006;22:205-12.

[15.] Kalkanli S, Ayyildiz O, Tiftik N, Batun S, Isikdogan A, Ince H, Tekes S, Muftuoglu E. Factor V Leiden mutation in venous thrombosis in southeast Turkey. Angiology 2006;57:193-6.

[16.] Gurlertop HY, Gundogdu F, Pirim I, Islamoglu Y, Egerci N, Sevimli S, Erdem F, Senocak H. Association between factor V Leiden mutation and coronary artery disease in the northeast region of Turkey. Blood Coagul Fibrinolysis 2007;18:719-22.

[17.] Ozbek U, Tangun Y. Frequency of factor V Leiden in Turkey. Br J Haemotol 1997;97:504-5.

[18.] Gul A, Ozbek U, Ozturk C, Inanc M, Konice M, Ozcelik T Coagulation factor V gene mutation increases the risk of venous thrombosis in Behcet's disease. Br J Rheumatol 1996;35:1178-80.

[19.] Berber E, Kavakli K, Akar N, Berber E, Caglayan SH. R506Q (FV Leiden) and R485K mutations in the factor V gene: incidence in deep venous thrombosis and hemophilia A patients. Turk J Hematol 2003;20:221-5.

[20.] Hobikoglu GF Akyuz U, Akyuz F, Ozer O, Guney D, Narin A, Unaltuna N. Factor V Leiden is a risk factor for myocardial infarction in young Turkish men. Acta Cardiol 2004;59:594-7.

[21.] Dolek B, Eraslan S, Eroglu S, Kesim BE, Ulutin T, Yalciner A, Laleli YR, Gozukirmizi N. Molecular analysis of factor V Leiden, factor V Hong Kong, factor II G20210A, methylenetetrahydrofolate reductase C677T and A1298C mutations related to Turkish thrombosis patients. Clin Appl Thromb Hemost 2007;13:435-8.

[22.] Okumus G, Kiyan E, Arseven O, Tabak L, Diz-Kucukkaya R, Unlucerci Y, Abaci N, Onaltuna NE, Issever H. Hereditary thrombotic risk factors and venous thromboembolism in Istanbul, Turkey: the role in different clinical manifestations of venous thromboembolism. Clin Appl Thromb Hemost 2008; 14:168-73.

[23.] Colak Y, Karasu Z, Oruc N, Can C, Balym Z, Akarca U, Gunsar F, Ersoz G, Tokat Y, Batur Y. Hyperhomocysteinaemia and factor V Leiden mutation are associated with Budd-Chiari syndrome. Eur J Gastroenterol Hepatol 2006;18:917-20.

[24.] Payzin B, Adakan FY, Yalcin HC, Cetinkaya GS, Berkmen S, Eraslan S, Unsal B. Natural coagulation inhibitory proteins and activated protein C resistance in Turkish patients with inflammatory bowel disease. Turk J Gastroenterol 2006;17:183-90.

[25.] Gorur K, Tuncer U, Eskandari G, Ozcan C, Onal M, Ozsahinoglu C. The role of factor V Leiden and prothrombin G2021 0a mutations in sudden sensorineural hearing loss. Otol Neurotol 2005;26:599-601.

[26.] Altintas A, Pasa S, Akdeniz N, Cil T, Yurt M, Ayyildiz O, Batun S, Isi H. Factor V Leiden and G20210A prothrombin mutations in patients with recurrent pregnancy loss: data from the southeast of Turkey. Ann Hematol 2007;86:727-31.

[27.] Kurt C, Tannverdi K, Kocak R. The frequency of factor V Leiden in southern Turkey. Ann Med Sci 1999;8:56.

[28.] Celik S, Ovali E, Baykan M, Ucar F, Erdol C, Durmus I, Kaplan S. Factor V Leiden and its relation to left ventricular thrombus in acute myocardial infarction. Acta Cardiol 2001;56:1-6.

[29.] Vurkun M, Vural O, Demir M. The prevalence of activated protein C resistance and F V Leiden in healthy population of Edirne, Turkey. Turk J Hematol 2002;19:287.

[30.] Atasay B, Arsan S, Gunlemez A, Kemahli S, Akar N. Factor V Leiden and prothrombin gene 20210A variant in neonatal thromboembolism and in healthy neonates and adults: a study in a single center. Pediatr Hematol Oncol 2003;20:627-34.

[31.] Baytan B, Meral AG, Ilcol YO, Gunay 0. The prevalence of factor V Leiden (1691 G-A) and methylenetetrahydrofolate reductase C677T mutations in healthy newborns in Bursa, Turkey. Turk J Hematol 2007;24:90-2.

[32.] Akar N. Frequency of hereditary thrombophilia in the Turkish population (effect of the age and genetic polymorphisms on the occurrence of thrombosis. Turk J Hematol 2000;17:3 (Suppl):230-3.

[33.] Chaida C, Gialeraki A, Tsoukala C, Mandalaki T Prevalence of the FVQ506 mutation in the Hellenic population. Thromb Haemost 1994;73:739-42.

[34.] Cin S, Akar N, Arcasoy A, Dedeoglu S, Cavdar AO. Prevalence of thalassemia and G6PD deficiency in North Cyprus. Acta Haematol 1984;71:69-70.

Nejat Akar

Department of Pediatric Molecular Genetics, Ankara University, School of Medicine, Ankara, Turkey
Table 1. Distribution of factor V Leiden among
the Turkish population

Region Number FV 1691 A
 of controls

Adana 77 4
Ankara 285 28
Ankara 81 6
Ankara 50 3
Ankara 80 5
Ankara 100 4
Aydin 47 2
Black Sea 103 16
Denizli 1030 87
Diyarbakir 151 7
Diyarbakir 320 29
Diyarbakir 27 3
Erzurum 78 0
Istanbul 120 11
Istanbul 107 11
Istanbul 86 8
Istanbul 66 6
Istanbul 114 4
Istanbul 191 17
I zmir 33 5
I zmir 37 0
Mersin 95 5
South East 185 13
Southern 264 23
Trabzon 95 7
Trace 476 20
Turkish Cypriots 99 12

Region % Reference

Adana 5.2 4
Ankara 9.8 5.3
Ankara 7.1 6
Ankara 6.0 7
Ankara 6.25 8
Ankara 4 9
Aydin 4.3 10
Black Sea 15 11
Denizli 8.41 12
Diyarbakir 4.6 13
Diyarbakir 9.1 14
Diyarbakir 11.1 15
Erzurum 0 16
Istanbul 9.2 17
Istanbul 10.3 18
Istanbul 9.3 19
Istanbul 9 20
Istanbul 3.5 21
Istanbul 8.9 22
I zmir 7.6 23
I zmir 0 24
Mersin 5.26 25
South East 7 26
Southern 8.7 27
Trabzon 7.3 28
Trace 4.28 29
Turkish Cypriots 12.2 5

Table 2. Distribution of factor V Leiden among Turkish newborns

Region n FV 1691 A % Reference

Ankara 137 15 11.9 30
Bursa 250 26 10.4 31
Balkan immigrants 137 15 10.9
Others 123 10 8
COPYRIGHT 2008 Aves Yayincilik
No portion of this article can be reproduced without the express written permission from the copyright holder.
Copyright 2008 Gale, Cengage Learning. All rights reserved.

Article Details
Printer friendly Cite/link Email Feedback
Author:Akar, Nejat
Publication:Turkish Journal of Hematology
Article Type:Report
Geographic Code:7TURK
Date:Mar 1, 2008
Previous Article:Brilliant cresyl blue staining for screening hemoglobin H disease: Reticulocyte smear/ Hemoglobin H hastaliginda goruntuleme icin brilliant cresyl...
Next Article:The estimation of platelet count from a blood smear on the basis of the red cell: platelet ratio/ Kan yaymasinda eritrosit ve trombosit orani...

Terms of use | Privacy policy | Copyright © 2019 Farlex, Inc. | Feedback | For webmasters