en fr Identification of genetic factors of two intermediary phenotypes of the venous thromboembolism : the levels of factors VIII and von Willebrand Identification de facteurs génétiques modulant deux phénotypes intermédiaireReport as inadecuate




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1 Génomique cardiovasculaire

Abstract : The Venous Thromboembolism VTE risk factors are environmental and genetic. The well established risk factors are anti-thrombin, protein C, protein S deficiency, Factor V Leiden and factor II mutation and ABO gene, with A1 and B allele increasing the risk of VTE. While an important part of VTE heritability remains unexplained, contemporary studies fail to discover new susceptibility genes with weaker effects. In order to increase the discovery power, I searched for genetic geterminism of two intermediary phenotypes of VTE : Factor VIII plasmatic activity FVIII and von Willebrand factor antigenemia vWFFirst, I performed a linkage study of FVIII and vWF from a sample of 5 large pedigrees N=255. Four loci have been identified. One included ABO gene. I searched for candidate genes located in the others loci by studying in silico results from o Genome Wide Association Study GWAS of the VTE including 419 cases and and 1228 controls. témoins. Two candidate genes were identified : STAB2 et BAI3. Then I performed association studies of five SNPs in BAI3 with FVIII and vWF. One of them was associated to vWF in a sample of 108 nuclear families and 916 VTE patients, and associated to VTE in two case-controls samples respectively 916 cases and 801 controls, and 250 cases et 607 controls.Second, I performed a meta-analysis of three GWAS of FVIII and vWF from the same 5 pedigrees and two samples of VTE N=972 and 570 adjusted on ABO blood group. No polymorphisms were significant after Bonferoni correction p



Author: Guillemette Antoni -

Source: https://hal.archives-ouvertes.fr/



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