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Interleukin-10 promoter microsatellite polymorphisms influence the immune response to heparin and the risk of heparin-induced thrombocytopenia.

Authors: Pouplard, C  Cornillet-Lefebvre, P  Attaoua, R  Leroux, D  Lecocq-Lafon, C  Rollin, J  Grigorescu, F  Nguyen, P  Gruel, Y 
Citation: Pouplard C, etal., Thromb Res. 2012 Apr;129(4):465-9. doi: 10.1016/j.thromres.2011.09.033. Epub 2012 Jan 10.
Pubmed: (View Article at PubMed) PMID:22239992
DOI: Full-text: DOI:10.1016/j.thromres.2011.09.033

INTRODUCTION: 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. MATERIALS AND 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). CONCLUSION: These results suggest that IL10 promoter microsatellite polymorphisms might influence the immune response against PF4/heparin and the risk of HIT.

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CRRD Object Information
CRRD ID: 11049164
Created: 2016-04-05
Species: All species
Last Modified: 2016-04-05
Status: ACTIVE



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RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.