Polymorphisms in the Prothrombin Gene and their Association with Plasma Prothrombin Levels

H. Ceelie; R. M. Bertina; A. van Hylckama Vlieg; F. R. Rosendaal; H. L. Vos

doi:10.1055/s-0037-1615965

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2001; 85(06): 1066-1070
DOI: 10.1055/s-0037-1615965

Review Article

Schattauer GmbH

Polymorphisms in the Prothrombin Gene and their Association with Plasma Prothrombin Levels

Authors

H. Ceelie

¹Haemostasis and Thrombosis Research Centre, Dept. of Haematology, Leiden, The Netherlands
R. M. Bertina

¹Haemostasis and Thrombosis Research Centre, Dept. of Haematology, Leiden, The Netherlands
A. van Hylckama Vlieg

¹Haemostasis and Thrombosis Research Centre, Dept. of Haematology, Leiden, The Netherlands

²Dept. of Clinical Epidemiology, Leiden University Medical Centre, Leiden, The Netherlands
F. R. Rosendaal

¹Haemostasis and Thrombosis Research Centre, Dept. of Haematology, Leiden, The Netherlands

²Dept. of Clinical Epidemiology, Leiden University Medical Centre, Leiden, The Netherlands
H. L. Vos

¹Haemostasis and Thrombosis Research Centre, Dept. of Haematology, Leiden, The Netherlands

Abstract

Summary

To find genetic causes of high plasma prothrombin levels, an established prothrombotic risk factor, we searched for sequence variations in the prothrombin gene. We selected subjects with the 20210-GG genotype (since the 20210-A allele is already known to be associated with high levels) and elevated prothrombin levels (≥ 130 U/dl) from the Leiden Thrombophilia Study (LETS). No mutations were found in the 1 kb promoter region of the prothrombin gene in seven individuals with an isolated high prothrombin level. Comparison of the allelic frequencies of four different polymorphisms in the prothrombin gene in healthy volunteers and in the control subjects among the selected LETS individuals indicated a higher frequency of the 19911-G allele in the latter group (allele frequency 52 vs. 78%, respectively). Homozygous carriers of the 19911-G allele had 8 U/dl higher plasma prothrombin levels than 19911-AA carriers. This difference in prothrombin levels did not affect the thrombotic risk in 20210-GG carriers. In heterozygous 20210-A carriers the odds ratio increased from 1.6 (95% CI: 0.6-4.3) in subjects with 19911-A to 4.7 (1.6-14.0) in subjects with 19911-G on the other prothrombin allele.

Key words

Prothrombin - G20210A - A19911G - venous thrombosis

Full Text

References

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