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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


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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
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Author:Akar, Nejat
Publication:Turkish Journal of Hematology
Article Type:Report
Geographic Code:7TURK
Date:Mar 1, 2008
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