Geographic Distribution of the 20210 G to A Prothrombin Variant
F. R. Rosendaal (1), (2), C. J. M. Doggen (1), A. Zivelin (3), V. R. Arruda (4), M. Aiach (5), D. S. Siscovick (6), A. Hillarp (7), H. H. Watzke (8), F. Bernardi (9), A. M. Cumming (10), F. E. Preston (11), P. H. Reitsma (12)
From the (1) Department of Clinical Epidemiology, Leiden University Medical Centre, Leiden, The Netherlands; (2) Department of Hematology, Leiden University Medical Centre, Leiden, The Netherlands; (3) Institute of Thrombosis and Hemostasis, Department
A variant in prothrombin (clotting factor II), a G to A transition at
nucleotide position 20210, has recently been shown to be associated
with the prothrombin plasma levels and the risk of both venous and
arterial thrombosis. The purpose of this study was to investigate the
prevalence of carriership of this mutation in various populations.
We combined data from 11 centres in nine countries, where tests
for this mutation had been performed in groups representing the
general population. We calculated an overall prevalence estimate, by a
precision-weighted method, and, since the distribution of the prevalences
did not appear homogeneous, by an unweighted average of
the prevalences. We examined differences in the prevalences by
geographical location and ethnic background as a possible explanation
for the heterogeneity.
Among a total of 5527 individuals who had been tested, 111 heterozygous
carriers of the 20210A mutation were found. The prevalence
estimates varied from 0.7 to 4.0 between the centres. The overall
prevalence estimate was 2.0 percent (CI95 1.4-2.6%). The variation
around the summary estimate appeared more than was expected by
chance alone, and this heterogeneity could be explained by geographic
differences. In southern Europe, the prevalence was 3.0 percent (CI95
2.3 to 3.7%), nearly twice as high as the prevalence in northern Europe
(1.7%, CI95 1.3 to 2.2%). The prothrombin variant appeared very rare
in individuals from Asian and African descent.
The 20210A prothrombin variant is a common abnormality, with a
prevalence of carriership between one and four percent. It is more
common in southern than in northern Europe. Since this distribution
within Europe is very different to that of another prothrombotic mutation (factor V Leiden or factor V R506Q), founder effects are the most
likely explanation for the geographical distribution of both mutations.