title: The factor V HR2 haplotype: prevalence and association of the A4070G and A6755G polymorphisms.
abstract: Recently, a polymorphism was identified in exon 25 of the factor V gene that is possibly a functional candidate for the HR2 haplotype. This haplotype is characterized by a single base substitution named R2 (A4070G) in the B domain of the protein. A mutation (A6755G; 2194Asp-->Gly) located near the C terminus has been hypothesized to influence protein folding and glycosylation, and might be responsible for the shift in factor V isoform (FV1 / FV2) ratio. This study investigated the prevalence of these two factor V HR2 haplotype polymorphisms in a cohort of normal blood donors, patients with osteoarthritis and women with complications during pregnancy, and in families of factor V Leiden individuals. A high allele frequency for the two polymorphisms was found in the blood donor group (6.2% R2, 5.6% A6755G). No significant difference in allele frequency was observed in the clinical groups (obstetric complications and osteoarthritis, 4.1-4.9% for the two polymorphisms) when compared with that of healthy blood donors. We confirm that the factor V A6755G polymorphism shows strong linkage to the R2 allele, although it is not exclusively inherited with the exon 13 A4070G variant and can occur independently.
authors: Co-operative Research Centre for Diagnostic Technologies, School of Life Sciences, Queensland University of Technology, Brisbane, Australia.
authors: N M
authors: NM
authors: Pecheniuk
authors: C P
authors: CP
authors: Morris
authors: T P
authors: TP
authors: Walsh
authors: N A
authors: NA
authors: Marsh
mesh_terms: D000483:Alleles; D019943:Amino Acid Substitution; D001782:Blood Donors; D015331:Cohort Studies; D015252:Deoxyribonucleases, Type II Site-Specific / Q000378:metabolism; D005091:Exons / Q000235:genetics*; D005165:Factor V / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D005192:Family Health; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D008297:Male; D010003:Osteoarthritis / Q000235:genetics; D010766:Phosphorylation; D017354:Point Mutation; D011110:Polymorphism, Genetic; D011247:Pregnancy; D011248:Pregnancy Complications; D015995:Prevalence; D017510:Protein Folding; D020033:Protein Isoforms / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D011499:Protein Processing, Post-Translational / Q000235:genetics; D017434:Protein Structure, Tertiary; D013379:Substrate Specificity
chemical_list: D020033:Protein Isoforms; C095381:factor V Leiden; D005165:Factor V; D015252:Deoxyribonucleases, Type II Site-Specific; C040158:GTAC-specific type II deoxyribonucleases