title: Polymorphism in factor VII gene modifies phenotype of severe haemophilia.
abstract: The basis for 10-15% of patients with severe haemophilia having clinically mild disease is not fully understood. We hypothesized that polymorphisms in various coagulant factors may affect frequency of bleeding while functionally significant polymorphisms in inflammatory and immunoregulatory genes may also contribute to variations in the extent of joint damage. These variables were studied in patients with severe haemophilia, who were categorized as 'mild' (<5 bleeds in the preceding year, <10 World Federation of Haemophilia clinical and <10 Pettersson scores, n = 14) or 'severe' (all others, n = 100). A total of 53 parameters were studied in each individual for their association with the clinical severity. Age, F8:c activity and the incidence of thrombotic markers were comparable between the groups while the median number of bleeds, number of affected joints, clinical, radiological and functional joint scores (P < or = 0.001) and life-time clotting factor use (P < or = 0.007) were different. Patients with severe molecular defects had a 4.1-fold increased risk for a severe phenotype (95% CI: 1.18-14.42, P = 0.026) compared with other mutations. Of the polymorphisms studied, the FVII353Q (RR = 3.5, 95% CI: 1.04-12.05, P = 0.044) allele was associated with a severe phenotype. This data shows that apart from the F8/F9 genotype, functional polymorphisms in FVII gene affect the phenotype of patients with severe haemophilia.
authors.affiliation: Departments of Haematology, Christian Medical College, Vellore, India.
authors.forename: G R
authors.initials: GR
authors.lastname: Jayandharan
authors.forename: S C
authors.initials: SC
authors.lastname: Nair
authors.forename: P M
authors.initials: PM
authors.lastname: Poonnoose
authors.forename: R
authors.initials: R
authors.lastname: Thomas
authors.forename: J
authors.initials: J
authors.lastname: John
authors.forename: S K
authors.initials: SK
authors.lastname: Keshav
authors.forename: R S
authors.initials: RS
authors.lastname: Cherian
authors.forename: M
authors.initials: M
authors.lastname: Devadarishini
authors.forename: K M
authors.initials: KM
authors.lastname: Lakshmi
authors.forename: R V
authors.initials: RV
authors.lastname: Shaji
authors.forename: A
authors.initials: A
authors.lastname: Viswabandya
authors.forename: B
authors.initials: B
authors.lastname: George
authors.forename: V
authors.initials: V
authors.lastname: Mathews
authors.forename: M
authors.initials: M
authors.lastname: Chandy
authors.forename: A
authors.initials: A
authors.lastname: Srivastava
mesh_terms: D000293:Adolescent; D000328:Adult; D015415:Biomarkers; D001779:Blood Coagulation Factors / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D005167:Factor VII / Q000235:genetics*; D056726:Genetic Association Studies; D005838:Genotype; D006467:Hemophilia A / Q000235:genetics*; D002836:Hemophilia B / Q000235:genetics*; D006470:Hemorrhage / Q000209:etiology / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D011110:Polymorphism, Genetic / Q000235:genetics*; D012720:Severity of Illness Index; D055815:Young Adult
chemical_list: D015415:Biomarkers; D001779:Blood Coagulation Factors; D005167:Factor VII