Feroza Dawood1, Roger Mountford, Roy Farquharson, Siobhan Quenby. 1. Department of Reproductive and Developmental Health, Liverpool Women's Hospital, University of Liverpool, Crown Street, Liverpool L8 7SS, UK. fdawood@liv.ac.uk
Abstract
BACKGROUND: Recurrent miscarriage (RM) has been associated with the thrombophilia, activated protein C resistance (APCR). The factor V Leiden mutation located on the B domain of the factor V gene, causes 95% of APCR and since the B domain is pivotal to APCR, it seemed plausible that other mutations or polymorphisms affecting this active domain may instigate acquired APCR. The objective of this study was to determine whether other polymorphisms exist on the parts of the gene encoding the B domain of the factor V in women with acquired APCR and RM. METHODS: There were 51 women with RM and acquired APCR, 24 parous women (with no history of miscarriage and at least one normal full-term delivery) and 15 women with a history of idiopathic RM, who formed the study and two control groups, respectively. Six exons of the B domain of the factor V gene were intensely analysed using polymerase chain reactions, single-strand conformation polymorphism, genetic sequencing and restriction enzyme digestion analysis to identify single-nucleotide polymorphisms (SNPs). RESULTS: A significantly increased frequency of some SNPs on the factor V gene were observed in the women with acquired APCR and RM when compared with the control groups. CONCLUSIONS: The presence of some of these SNPs may predispose these women to acquired APCR and RM.
BACKGROUND: Recurrent miscarriage (RM) has been associated with the thrombophilia, activated protein C resistance (APCR). The factor V Leiden mutation located on the B domain of the factor V gene, causes 95% of APCR and since the B domain is pivotal to APCR, it seemed plausible that other mutations or polymorphisms affecting this active domain may instigate acquired APCR. The objective of this study was to determine whether other polymorphisms exist on the parts of the gene encoding the B domain of the factor V in women with acquired APCR and RM. METHODS: There were 51 women with RM and acquired APCR, 24 parous women (with no history of miscarriage and at least one normal full-term delivery) and 15 women with a history of idiopathic RM, who formed the study and two control groups, respectively. Six exons of the B domain of the factor V gene were intensely analysed using polymerase chain reactions, single-strand conformation polymorphism, genetic sequencing and restriction enzyme digestion analysis to identify single-nucleotide polymorphisms (SNPs). RESULTS: A significantly increased frequency of some SNPs on the factor V gene were observed in the women with acquired APCR and RM when compared with the control groups. CONCLUSIONS: The presence of some of these SNPs may predispose these women to acquired APCR and RM.
Authors: Guojie Zhang; Zhang Pei; Edward V Ball; Matthew Mort; Hildegard Kehrer-Sawatzki; David N Cooper Journal: Hum Genomics Date: 2011-07 Impact factor: 4.639