title: Identification of a new SERPINC1 mutation in a Kazak family that alters the heparin binding capacity of antithrombin.
abstract: BACKGROUND
  Given its central role in mediating heparin-induced anti-coagulation, antithrombin (AT) gene mutations may result in heparin resistance. This study investigates the relationship between familial AT gene mutations and tolerance to heparin.
  
  
  METHODS
  The medical history of a male patient with heparin resistance who received heart surgery and six of his family members was reviewed. Activated partial thromboplastin time (APTT), prothrombin time (PT), fibrinogen (Fib), D-dimer (D=D), and platelet count were determined to assess coagulation function. AT activity and the AT gene were also analyzed. For the newly identified gene mutations, polymorphisms were excluded in 120 healthy Kazak controls.
  
  
  RESULTS
  Two mutations were identified in exon 7 of the AT gene, SERPINC1: g.1267G>A (p.A391T) found in five participants, including the index patient, and g.1334G>A, a silent mutation, in two family members. The g.1267G>A mutation may alter focal AT protein conformation. Neither of these mutations was observed in the healthy Kazak controls. Although all coagulation parameters and AT activity were within the normal ranges for the index patient and his family members, the platelet levels were significantly lower than that observed for the healthy Kazak controls (p=0.001). There was no significant difference in AT antigen levels between the groups; however, participants with the g.1267G>A mutation had a 44.25% reduction in heparin binding compared to the control group (p<0.001).
  
  
  CONCLUSIONS
  We identified a novel hereditary mutation, g.1267G>A (p.A391T), in the AT gene, which reduces its heparin binding capacity and might be associated with resistance to heparin.
authors.affiliation: Department of Anesthesiology, The First Affiliated Hospital of Xinjiang Medical University, Urumqi 830054, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Zheng
authors.affiliation: Department of Anesthesiology, The First Affiliated Hospital of Xinjiang Medical University, Urumqi 830054, China.
authors.forename: Hai-Ping
authors.initials: HP
authors.lastname: Ma
authors.affiliation: Department of Anesthesiology, The First Affiliated Hospital of Xinjiang Medical University, Urumqi 830054, China.
authors.forename: Wei-fang
authors.initials: WF
authors.lastname: Xu
authors.affiliation: Department of Anesthesiology, The First Affiliated Hospital of Xinjiang Medical University, Urumqi 830054, China.
authors.forename: Yong-Qiang
authors.initials: YQ
authors.lastname: Zhang
authors.affiliation: Department of Anesthesiology, The First Affiliated Hospital of Xinjiang Medical University, Urumqi 830054, China.
authors.forename: Jian-jiang
authors.initials: JJ
authors.lastname: Wu
authors.affiliation: Department of Anesthesiology, The First Affiliated Hospital of Xinjiang Medical University, Urumqi 830054, China. Electronic address: wangjiang@sina.cn.
authors.forename: Jiang
authors.initials: J
authors.lastname: Wang
mesh_terms: D000328:Adult; D000368:Aged; D000925:Anticoagulants / Q000276:immunology; D000990:Antithrombin III / Q000235:genetics* / Q000276:immunology*; D000991:Antithrombins / Q000276:immunology*; D001483:Base Sequence; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006493:Heparin / Q000276:immunology*; D006801:Humans; D007623:Kazakhstan; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D011485:Protein Binding; D011517:Prothrombin Time; D055815:Young Adult
chemical_list: D000925:Anticoagulants; D000991:Antithrombins; C542513:SERPINC1 protein, human; D000990:Antithrombin III; D006493:Heparin
keywords: Antithrombin; Coagulation; Heparin; Prothrombin time; Thromboplastin time