title: Interleukin-10 promoter microsatellite polymorphisms influence the immune response to heparin and the risk of heparin-induced thrombocytopenia.
abstract: BACKGROUND
  Heparin-induced thrombocytopenia (HIT) results from an atypical immune response with synthesis of IgG antibodies (Abs) to platelet factor 4/heparin complexes (PF4/H), and probably involves both B and T cells. We investigated whether 3 single nucleotide polymorphisms (SNPs), rs1800896 (-1082G/A), rs1800871 (-819C/T) and rs1800872 (-592C/A) and the polymorphic CA repeat microsatellites IL10R [5325CA(11_15)] and IL10G [8134CA(14_29)] are associated with the synthesis of Abs to PF4/heparin and HIT.
  
  
  METHODS
  Eighty-two patients with definite HIT and two control groups were studied. The first control group (Ab(neg)) consisted of 85 patients without Abs to PF4/heparin after cardiopulmonary bypass (CPB). The second control group (Ab(pos)) consisted of 84 patients who had developed significant levels of PF4-specific antibodies after CPB, but without HIT.
  
  
  RESULTS
  Allele frequencies of the 3 SNPs were similar in HIT patients and controls. Fourteen alleles in IL10G (G16 to G29) and 3 alleles in IL10R (R13 to R15) were defined. The short G20 allele of IL10G was more frequent in Ab(neg) patients (8.2%) than in Ab(pos) (2.9%) and HIT patients (3%). It thereby appeared to protect against developing Abs to PF4/heparin (OR 0.29; 95% CI [0.12-0.70], p=0.006). Combined haplotypes cH1/cH8 comprising the short G20 + R13 alleles were less frequent in HIT (OR 0.33; 95% CI [0.11-0.97], p=0.036), and levels of Abs to PF4 in Ab(pos) patients were lower in cH1/cH8 subjects (p=0.019).
  
  
  CONCLUSIONS
  These results suggest that IL10 promoter microsatellite polymorphisms might influence the immune response against PF4/heparin and the risk of HIT.
authors.affiliation: Department of Hematology-Hemostasis, University Hospital of Tours, France.
authors.forename: Claire
authors.initials: C
authors.lastname: Pouplard
authors.forename: Pascale
authors.initials: P
authors.lastname: Cornillet-Lefebvre
authors.forename: Redha
authors.initials: R
authors.lastname: Attaoua
authors.forename: Dorothée
authors.initials: D
authors.lastname: Leroux
authors.forename: Carinne
authors.initials: C
authors.lastname: Lecocq-Lafon
authors.forename: Jérôme
authors.initials: J
authors.lastname: Rollin
authors.forename: Florin
authors.initials: F
authors.lastname: Grigorescu
authors.forename: Philippe
authors.initials: P
authors.lastname: Nguyen
authors.forename: Yves
authors.initials: Y
authors.lastname: Gruel
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D005602:France / Q000453:epidemiology; D006493:Heparin / Q000009:adverse effects* / Q000627:therapeutic use; D006801:Humans; D007113:Immunity, Innate / Q000187:drug effects* / Q000235:genetics / Q000276:immunology; D016753:Interleukin-10 / Q000235:genetics* / Q000276:immunology; D008297:Male; D018895:Microsatellite Repeats / Q000235:genetics; D008875:Middle Aged; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D015995:Prevalence; D011401:Promoter Regions, Genetic / Q000235:genetics*; D018570:Risk Assessment; D012307:Risk Factors; D013921:Thrombocytopenia / Q000139:chemically induced* / Q000453:epidemiology / Q000235:genetics / Q000276:immunology*
chemical_list: C508609:IL10 protein, human; D016753:Interleukin-10; D006493:Heparin