title: Three novel variants in the coagulation factor V gene associated with deep venous thrombosis in Chilean patients with Amerindian ethnic background.
abstract: BACKGROUND
  The activated protein C (APC) resistance is the most common prothrombotic defect in thrombosis patients, mainly related with alterations in the F5 gene. In this work, we evaluated the presence of variants in the FV gene in Amerindian patients with deep venous thrombosis and APC resistance.
  
  
  METHODS
  A total of 87 patients with deep venous thrombosis (DVT) confirmed by Doppler ultrasonography, and Amerindian genetic background, were included in this study. APC resistance was assayed by clotting methods and polymorphism F51691G>A was genotyped by molecular methods. In Amerindian patients with APC resistance, the promoter region, exon 7 and exon 10 of the F5 gene were screened by PCR-SSCP and DNA sequencing. The prediction of functional effect of novel mutations was analyzed using Polyphen-2 software.
  
  
  RESULTS
  In DVT patients, 14.9% showed functional APC resistance in the absence of F51691G>A polymorphism. Interestingly, three novel missense mutations in exon 10 of F5 gene (M443L, E461Q and G493E) were identified. These genetic variants were absent in 100 healthy subjects. According to in silico analysis, the sequence variants G493E and E461Q are potentially deleterious.
  
  
  CONCLUSIONS
  Our data shows that the APC resistance phenotype is not associated with the presence of the F51691G>A variant. We described, for the first time, the presence of three novel variants in F5 gene in Chilean patients with APC resistance. Further studies are required to investigate the real contribution of these novel mutations to the APC resistance phenotype.
authors: Center of Molecular Biology and Pharmacogenetics, Scientific and Technological Bioresource Nucleus (BIOREN), Universidad de La Frontera, Temuco, Chile; Escuela de Ciencias de la Salud, Universidad Católica de Temuco, Temuco, Chile; Laboratorio de Diagnóstico Molecular, Facultad de Ciencias de la Salud, Universidad San Sebastián, Concepción, Chile.
authors: Neftalí
authors: N
authors: Guzmán
authors: Centro de Excelencia de Modelación y Computación Científica, Facultad de Ingeniería y Ciencias, Universidad de La Frontera, Temuco, Chile.
authors: Giovanni
authors: G
authors: Larama
authors: Centro de Excelencia de Modelación y Computación Científica, Facultad de Ingeniería y Ciencias, Universidad de La Frontera, Temuco, Chile.
authors: Andrés
authors: A
authors: Ávila
authors: Center of Molecular Biology and Pharmacogenetics, Scientific and Technological Bioresource Nucleus (BIOREN), Universidad de La Frontera, Temuco, Chile. Electronic address: luis.salazar@ufrontera.cl.
authors: Luis A
authors: LA
authors: Salazar
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D002677:Chile; D005006:Ethnicity / Q000235:genetics*; D005165:Factor V / Q000235:genetics* / Q000378:metabolism; D005260:Female; D014644:Genetic Variation / Q000235:genetics*; D006801:Humans; D007199:Indians, South American / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D011486:Protein C / Q000235:genetics*; D020246:Venous Thrombosis / Q000097:blood / Q000175:diagnosis / Q000235:genetics*; D055815:Young Adult
chemical_list: D011486:Protein C; D005165:Factor V
keywords: Coagulation factor V; Deep venous thrombosis; Risk factors; Thrombophilia