title: [Relationship between factor VIII inhibitor development and polymorphisms of TNFα and CTLA-4 gene in Chinese Han patients with hemophilia A].
abstract: OBJECTIVE
  To investigate the potential association between factor VIII inhibitor development and polymorphisms of tumor necrosis factor-α (TNF-α)-308 and cytotoxic T-lymphocyte associated protein-4 gene in Chinese Han patients with hemophilia A (HA).
  
  
  METHODS
  The single base change polymorphism in TNF-α and CTLA-4 gene was analyzed in 140 Chinese Han patients with hemophilia A who have been treated with plasma-derived FVIII concentrates and 108 normal controls by using PCR-restrictive fragment length polymorphism (RFLP). All of the HA patients' plasma samples were measured by modified-Nijmegen assay simultaneously.
  
  
  RESULTS
  In HA patients, G/G genotype, G/A genotype and A/A genotype were detected in 118 (84.3%), 18 (12.8%) and 4 cases (2.9%) respectively; C/C genotype, C/T genotype and T/T genotype were detected in 108 (77.2%), 30 (21.4%) and 2 cases (1.4%) respectively. The difference in the genotype frequencies between HA patients and controls was nonsignificant (P > 0.05). Patients who were carriers of homozygotes for A allele had a higher risk of inhibitor development compared with those who were not (OR = 7.519, 95% CI = 3.168 - 17.844). Severe HA patients who were carriers of homozygotes for A allele had a higher risk of inhibitor development compared with those who were not (OR = 8.163, 95% CI = 2.521 - 26.434). There was no statistical difference in the risk of inhibitor development between the patients who were carriers or not (OR = 1.586, 95% CI = 0.729 - 3.450).
  
  
  CONCLUSIONS
  TNF-α-308 gene polymorphism is significantly associated with inhibitor development in Chinese Han patients with severe hemophilia A. TNF-α gene may be a useful marker and potential modulator of the immune response to replacement therapy for hemophilia A patients.
authors.affiliation: Jiangsu Institute of Hematology, the First Affiliated Hospital of Soochow University, Key Laboratory of Thrombosis and Hemostasis of Ministry of Health, Suzhou 215006, China.
authors.forename: Lu-lu
authors.initials: LL
authors.lastname: Zhang
authors.forename: Zi-qiang
authors.initials: ZQ
authors.lastname: Yu
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.forename: Li-juan
authors.initials: LJ
authors.lastname: Cao
authors.forename: Jian
authors.initials: J
authors.lastname: Su
authors.forename: Xia
authors.initials: X
authors.lastname: Bai
authors.forename: Chang-geng
authors.initials: CG
authors.lastname: Ruan
mesh_terms: D000293:Adolescent; D000328:Adult; D044466:Asian People / Q000235:genetics; D060908:CTLA-4 Antigen / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D005838:Genotype; D006467:Hemophilia A / Q000235:genetics*; D006801:Humans; D007223:Infant; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*; D055815:Young Adult
chemical_list: D060908:CTLA-4 Antigen; D014409:Tumor Necrosis Factor-alpha