title: Glanzmann's thrombasthenia: modulation of clinical phenotype by alpha2C807T gene polymorphism.
abstract: OBJECTIVE
  The expression of Glanzmann's thromboasthenia (GT) varies, even among patients carrying the same mutation. It is conceivable that other gene loci may influence the clinical expression of GT and lead to specific phenotypes.
  
  
  METHODS
  To investigate GT clinical heterogeneity we screened 25 GT patients with a known alpha(IIb)beta3 molecular defect for thrombophilic mutations (FV Leiden, FII A20210) and the platelet glycoprotein (GP) alpha2 C807T gene polymorphism.
  
  
  RESULTS
  The FV Leiden mutation was found in 1 patient, the FII A20210 mutation in none. Three GT patients were homozygous for the T807 allele and showed a mild clinical expression of GT whereas none of the patients presenting with a moderate or severe GT phenotype carried the alpha2 TT genotype (p=0.037, two-sided exact test). In patients carrying the same mutation, the clinical GT phenotype was milder in those with the TT807 genotype.
  
  
  CONCLUSIONS
  Since the platelet alpha2 C807T gene polymorphism is associated with alpha2beta1 receptor density on the platelet surface, our findings suggest that the level of alpha2beta1 on platelets may be an additional factor affecting GT clinical expression.
authors.affiliation: Unità di Aterosclerosi e Trombosi IRCCS Casa Sollievo della Sofferenza, viale Cappuccini, San Giovanni Rotondo, Foggia.
authors.forename: Giovanna
authors.initials: G
authors.lastname: D'Andrea
authors.forename: Maurizio
authors.initials: M
authors.lastname: Margaglione
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D000483:Alleles; D019943:Amino Acid Substitution; D005165:Factor V / Q000032:analysis / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006474:Hemorrhagic Disorders / Q000235:genetics; D006801:Humans; D038982:Integrin alpha2beta1 / Q000032:analysis* / Q000235:genetics; D008297:Male; D010641:Phenotype; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000235:genetics; D040201:Platelet Membrane Glycoprotein IIb / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D011516:Prothrombin / Q000235:genetics; D012720:Severity of Illness Index; D013329:Structure-Activity Relationship; D013915:Thrombasthenia / Q000235:genetics* / Q000473:pathology
chemical_list: D020413:3' Untranslated Regions; D038982:Integrin alpha2beta1; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D040201:Platelet Membrane Glycoprotein IIb; C095381:factor V Leiden; D005165:Factor V; D011516:Prothrombin