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A novel mutation of Arg306 of factor V gene in Hong Kong Chinese
1Department of Medicine, University of Hong Kong, Queen Mary Hospital, Hong Kong.
Insights
The common Arg 506 Gln mutation in the factor V gene is rare in Hong Kong Chinese. A novel Arg 306 Gly mutation in the factor V gene may be clinically significant for thrombosis risk.
Area of Science:
- Genetics
- Molecular Biology
- Thrombosis Research
Background:
- Factor V gene mutations are associated with an increased risk of venous thromboembolism.
- The Arg 506 Gln mutation is the most common genetic risk factor for activated protein C resistance.
- Prevalence of factor V gene variants can differ across ethnic populations.
Purpose of the Study:
- To investigate the prevalence of genetic variants in the factor V gene among Hong Kong Chinese individuals.
- To identify specific mutations associated with deep vein thrombosis in this population.
- To explore potential novel genetic risk factors for thrombosis.
Main Methods:
- Analysis of factor V gene exons 7, 10, and 13 in 83 Hong Kong Chinese subjects using denaturing gradient gel electrophoresis.
- Sequencing of specific codons (Arg306, Arg506, Arg679) known to harbor common mutations.
- Functional assessment of activated protein C resistance in a patient carrying a novel mutation.
Main Results:
- The G1691-->A (Arg 506-->Gln) mutation was not detected in any subjects.
- A high allelic frequency of the G1628-->A (Arg 485-->Lys) substitution was observed in exon 10.
- A novel mutation, A1090-->G in exon 7 (Arg 306-->Gly), was identified in two thrombotic patients and one non-thrombotic individual.
Conclusions:
- The common Arg 506-->Gln mutation is rare in the Hong Kong Chinese population.
- The novel Arg 306-->Gly mutation in the factor V gene may represent a significant genetic risk factor for thrombosis in this ethnic group.
- Further investigation into the Arg 306-->Gly substitution and its association with activated protein C resistance is warranted.
Abstract:
We have analyzed 83 unrelated Hong Kong Chinese for the presence of genetic variants of factor V gene. Forty-three of them had a history of deep vein thrombosis. The DNA sequence variations of exons 7, 10, and 13, where the codons for Arg306, Arg506, and Arg679 are located, respectively, were studied by denaturing gradient gel electrophoresis. The G1691-->A (Arg 506-->Gln) mutation in exon 10 was not detectable in any of the 83 subjects. However, a high allelic frequency for the G1628-->A (Arg 485-->Lys) substitution was detectable in the same exon. We have also identified a novel DNA sequence mutation (A1090-->G) in exon 7 that resulted in Arg 306-->Gly substitution in 2 thrombotic patients and 1 nonthrombotic subject. Fresh blood samples were available from one of them for analysis of activated protein C resistance and the result was negative. Variation of DNA sequence was not found in exon 13 in any of our 83 subjects. The results of this study showed that, although the Arg 506-->Gln mutation was rarely found in the Hong Kong Chinese population, a different mutation site such as A 1090-->G in exon 7 of the factor V gene (Arg 306) may be of clinical importance.