Functional polymorphisms of FGA, encoding α fibrinogen, are associated with susceptibility to venous thromboembolism in a Taiwanese population
| Autor: | Ming-Sheng Teng, Tsu-Shiu Hsu, Yu-Lin Ko, Chi-Jen Chang, Chia Ti Tsai, Lung-An Hsu, Semon Wu, Ying-Shiung Lee |
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| Rok vydání: | 2005 |
| Předmět: |
Adult
Male Linkage disequilibrium Genotype TaqI Recombinant Fusion Proteins DNA Mutational Analysis Population Taiwan Gene Expression Biology Fibrinogen chemistry.chemical_compound Gene Frequency Cell Line Tumor Thromboembolism Genetics medicine Humans Genetic Predisposition to Disease cardiovascular diseases Allele Luciferases Promoter Regions Genetic education Allele frequency Alleles Polymorphism Single-Stranded Conformational Genetics (clinical) Aged Venous Thrombosis education.field_of_study Polymorphism Genetic Haplotype Middle Aged equipment and supplies Protein Subunits Haplotypes chemistry Female medicine.drug |
| Zdroj: | Human Genetics. 119:84-91 |
| ISSN: | 1432-1203 0340-6717 |
| Popis: | To determine the genetic risk factors for venous thromboembolism (VTE), this study examined 14 genetic variants from 10 hemostatic genes in 186 Taiwanese VTE patients and the same number of matched controls, which demonstrated FGA (encoding alpha fibrinogen) Thr312Ala polymorphism was the only variant significantly associated with VTE. Nine genetic polymorphisms on the fibrinogen cluster region of chromosome 4q28 were further studied, in which four FGA polymorphisms were found in strong linkage disequilibrium and were significantly associated with VTE by genotype and allele frequency analyses. Haplotype analysis showed significantly different FGA haplotype frequencies between VTE patients and controls with the haplotype F1, containing -1051G, -3A, 312Ala and TaqI duplication alleles, significantly associated with susceptibility to VTE (P = 0.001). Haplotype-pair analysis results also indicated a strong association of the haplotype-pair F1F1 with VTE in various VTE patient subgroups. In vitro functional analysis indicated that FGA -1051G, -3A and TaqI duplication alleles enhanced significantly the transcription level of FGA; however, control subjects with FGA genotypes containing these alleles had no elevated plasma fibrinogen levels. In conclusion, our experimental data indicated that functional genetic variants in FGA are risk factors for VTE in Taiwanese populations. Determination of FGA genotypes will likely contribute to primary prevention of this condition. |
| Databáze: | OpenAIRE |
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