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  • The KIR2DS2/DL2 genotype is associated with adult persistent/chronic and relapsed immune thrombocytopenia independently of FCGR3a-158 polymorphisms

    Author(s)
    Nourse, Jamie P
    Lea, Rod
    Crooks, Pauline
    Wright, Gillian
    Huyen, Tran
    Catalano, John
    Brighton, Tim
    Grigg, Andrew
    Marlton, Paula
    Gandhi, Maher K
    Griffith University Author(s)
    Lea, Rodney A.
    Year published
    2012
    Metadata
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    Abstract
    Adult immune thrombocytopenia (ITP) is a heterogeneous disease and its immunobiology is incompletely understood. Establishing associations between candidate genes and ITP susceptibility may provide insight into pathogenesis. Previous studies have associated overrepresentation of FCGR3a-V158 allele with pediatric ITP. We prospectively accrued DNA from 102 adult patients with persistent/ chronic or relapsed primary ITP identified by defined criteria. The distribution of KIR2 genes and polymorphisms of FCGR3a, both associated with autoimmunity, were compared with 105 healthy white individuals. Results were stratified ...
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    Adult immune thrombocytopenia (ITP) is a heterogeneous disease and its immunobiology is incompletely understood. Establishing associations between candidate genes and ITP susceptibility may provide insight into pathogenesis. Previous studies have associated overrepresentation of FCGR3a-V158 allele with pediatric ITP. We prospectively accrued DNA from 102 adult patients with persistent/ chronic or relapsed primary ITP identified by defined criteria. The distribution of KIR2 genes and polymorphisms of FCGR3a, both associated with autoimmunity, were compared with 105 healthy white individuals. Results were stratified by ethnicity. Carriers of the KIR2DS2/KIR2DL2 genotype [KIR2DS2R/KIR2DL2R versus KIR2DS2S/ KIR2DL2R/S and KIR2DS2R/S/KIR2DL2S; odds ratio (OR) 2.51, PU0.002] were overrepresented. In addition, frequency of the high-binding affinity FCGR3a-V/V158 genotype (VV versus VF/FF; ORU3.05, PU0.007) was increased, whereas that of the FCGR3a-F158 allele was reduced (ORU2.58, PU0.00 002). In a regression model to adjust for age, sex and the effects of the other gene, the KIR2 genotype independently conferred increased susceptibility from the FCGR3a-158 polymorphisms. In a comparison of healthy controls and a tightly defined cohort of adult ITP patients, the KIR2DS2/KIR2DL2 genotype was found to be associated with ITP independently of FCGR3a- 158 polymorphisms. Further studies are required to establish the mechanistic basis for these observations and their potential impact on immune-based therapies.
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    Journal Title
    Blood Coagulation and Fibrinolysis
    Volume
    23
    Issue
    1
    DOI
    https://doi.org/10.1097/MBC.0b013e32834d7ce3
    Subject
    Clinical sciences
    Autoimmunity
    Publication URI
    http://hdl.handle.net/10072/45868
    Collection
    • Journal articles

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