title: Thrombophilic mutations among Southern Iranian patients with sickle cell disease: high prevalence of factor V Leiden.
abstract: BACKGROUND
  A hypercoagulable state in sickle cell disease (SCD) and beta thalassemia has been established and thrombosis is an important aspect of the clinical spectrum of sickle cell disease. In a case-control study, the prevalence of factor V Leiden and prothrombin G20210A mutations were investigated among SCD patients from Southern Iran.
  
  
  METHODS
  Patients comprised 60 individuals with SCD; of them 35 were with sickle cell anemia (SS) including 21 males and 14 females aged 17.2+/-8.3 years, 15 were sickle cell trait (AS) consisted of nine males and six females aged 30+/-15.4 years and 10 were sickle/beta thalassemia (S/Thal) (three males and seven females) aged 24.6+/-10.4 years. The control group were 126 apparently healthy individuals (50 males and 76 females) aged 20.1+/-9.8 years. Genotyping was done by polymerase chain reaction restriction fragment-length polymorphism (PCR-RFLP) using Mnl I and Hind III for factor V Leiden and prothrombin G20210A, respectively.
  
  
  RESULTS
  Heterozygous factor V Leiden mutation was found in five of 35 (14.3%) SS patients, two of 15 (13.3%) AS individuals, one (a sickle/beta-zero thalassemia patient with IVSII.1 G-->A mutation) of 10 S/Thal patients (10%), and two of 126 (1.6%) control subjects (P<0.05). However, only one AS individual (6.7%) was found to be a carrier for prothrombin G20210A compared to five of 126 (4%) healthy individuals. Adjusted logistic regression analysis for the effects of age and sex was performed and a significant association was found between factor V Leiden mutation and sickle cell anemia with odds ratios (OR) of 6.5 (95% confidence intervals [CI] 1.19-35.33, P=0.03) in SS patients. However, increased prevalence of the factor V Leiden in AS individuals and S/Thal patients was not statistically significant compared to controls (OR 3.84, 95% CI 0.49-29.9, P=0.19 and OR 3.77, 95% CI 0.31-45.9, P=0.29, respectively).
  
  
  CONCLUSIONS
  Our findings indicate a significant correlation between factor V Leiden and sickle cell anemia among Iranian patients. Association between venous thrombophilia and factor V Leiden mutation in Iranians with sickle cell anemia should be further studied.
authors.affiliation: Medical Biology Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran. zrahimi@kums.ac.ir
authors.forename: Zohreh
authors.initials: Z
authors.lastname: Rahimi
authors.forename: Asad
authors.initials: A
authors.lastname: Vaisi-Raygani
authors.forename: Ronald L
authors.initials: RL
authors.lastname: Nagel
authors.forename: Adriana
authors.initials: A
authors.lastname: Muniz
mesh_terms: D000293:Adolescent; D000328:Adult; D000755:Anemia, Sickle Cell / Q000097:blood / Q000208:ethnology / Q000235:genetics*; D001777:Blood Coagulation / Q000235:genetics*; D016022:Case-Control Studies; D002648:Child; D005165:Factor V / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006579:Heterozygote; D006801:Humans; D007492:Iran / Q000453:epidemiology; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D009154:Mutation; D016017:Odds Ratio; D012150:Polymorphism, Restriction Fragment Length; D011516:Prothrombin / Q000235:genetics; D018570:Risk Assessment; D012805:Sickle Cell Trait / Q000097:blood / Q000235:genetics; D019851:Thrombophilia / Q000097:blood / Q000208:ethnology / Q000235:genetics*; D017086:beta-Thalassemia / Q000097:blood / Q000235:genetics
chemical_list: C095381:factor V Leiden; D005165:Factor V; D011516:Prothrombin