title: Prevalence of Factor V Genetic Variants Associated With Indian APCR Contributing to Thrombotic Risk.
abstract: Phenotypic resistance to activated protein C (APC) is a complex mechanism associated with increased thrombosis risk. Activated protein C resistance (APCR) is mainly influenced by FVLeidenmutation, and various other single nucleotide polymorphisms (SNPs) in FV gene are known to be associated with APCR. The aim of present study was to investigate the incidence and assess possible mechanisms of APCR in Indian patients with deep vein thrombosis (DVT). Three hundred and ten Doppler-proven patients with DVT were screened for APCR, and 50 APCR positive patients and 50 controls were typed for FVLeiden, Hong Kong, Cambridge, HR2 haplotype, Glu666Asp, Ala485Lys, and Liverpool using either polymerase chain reaction (PCR)-restriction fragment length polymorphism or allele specific PCR. FVLeidenwas commonest cause of APCR (50%) in Indian patients with DVT being statistically significant ( P = .001) compared to controls. FV Liverpool, FV Glu666Asp and FV Ala485Lys were studied for the first time in Indian population. FV Liverpool, FV Glu666Asp, Hong Kong, and Cambridge were found to be absent. High frequency of Ala485Lys in patients shows that it might be a risk factor contributing to APCR in Indian patients with DVT. HR2 haplotype was not associated with APCR; however, presence of homozygous HR2 haplotype in patients only indicates the role it might play in Indian APCR population. In conclusion, contribution of FVLeidencausing APCR in Indian population is not as strong as previously reported in Western countries. The presence of other SNPs observed in the present study requires such studies on larger sample size to understand the molecular basis of defect.
authors.affiliation: 1 Department of Hematology, All India Institute of Medical Sciences, New Delhi, India.
authors.forename: Amit
authors.initials: A
authors.lastname: Sharma
authors.affiliation: 2 Protein Conformation and Enzymology Lab, Department of Biosciences, Jamia Millia Islamia, New Delhi, India.
authors.forename: Teena
authors.initials: T
authors.lastname: Bhakuni
authors.affiliation: 3 Institute of Experimental Haematology and Transfusion Medicine, University Clinic Bonn, Bonn, Germany.
authors.forename: Arijit
authors.initials: A
authors.lastname: Biswas
authors.affiliation: 1 Department of Hematology, All India Institute of Medical Sciences, New Delhi, India.
authors.forename: Ravi
authors.initials: R
authors.lastname: Ranjan
authors.affiliation: 1 Department of Hematology, All India Institute of Medical Sciences, New Delhi, India.
authors.forename: Ravi
authors.initials: R
authors.lastname: Kumar
authors.affiliation: 1 Department of Hematology, All India Institute of Medical Sciences, New Delhi, India.
authors.forename: Kamal
authors.initials: K
authors.lastname: Kishore
authors.affiliation: 1 Department of Hematology, All India Institute of Medical Sciences, New Delhi, India.
authors.forename: Manoranjan
authors.initials: M
authors.lastname: Mahapatra
authors.affiliation: 2 Protein Conformation and Enzymology Lab, Department of Biosciences, Jamia Millia Islamia, New Delhi, India.
authors.forename: Mohamad Aman
authors.initials: MA
authors.lastname: Jairajpuri
authors.affiliation: 1 Department of Hematology, All India Institute of Medical Sciences, New Delhi, India.
authors.forename: Renu
authors.initials: R
authors.lastname: Saxena
mesh_terms: D020016:Activated Protein C Resistance / Q000453:epidemiology / Q000235:genetics*; D000328:Adult; D044466:Asian People; D005165:Factor V / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease / Q000453:epidemiology*; D006801:Humans; D007194:India / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D015995:Prevalence; D013927:Thrombosis / Q000453:epidemiology / Q000235:genetics*; D055815:Young Adult
chemical_list: D005165:Factor V
keywords: activated protein C resistance; factor V; polymorphism; thrombosis