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

Nourse, Jamie P., Lea, Rod, Crooks, Pauline, Wright, Gillian, Tran, Huyen, Catalano, John, Brighton, Tim, Grigg, Andrew, Marlton, Paula and Gandhi, Maher K. (2012) The KIR2DS2/DL2 genotype is associated with adult persistent/chronic and relapsed immune thrombocytopenia independently of FCGR3a-158 polymorphisms. Blood Coagulation and Fibrinolysis, 23 1: 45-50. doi:10.1097/MBC.0b013e32834d7ce3


Author Nourse, Jamie P.
Lea, Rod
Crooks, Pauline
Wright, Gillian
Tran, Huyen
Catalano, John
Brighton, Tim
Grigg, Andrew
Marlton, Paula
Gandhi, Maher K.
Title The KIR2DS2/DL2 genotype is associated with adult persistent/chronic and relapsed immune thrombocytopenia independently of FCGR3a-158 polymorphisms
Journal name Blood Coagulation and Fibrinolysis   Check publisher's open access policy
ISSN 0957-5235
1473-5733
Publication date 2012-01
Year available 2011
Sub-type Article (original research)
DOI 10.1097/MBC.0b013e32834d7ce3
Volume 23
Issue 1
Start page 45
End page 50
Total pages 6
Place of publication Philadelphia, PA, United States
Publisher Lippincott Williams & Wilkins
Collection year 2012
Language eng
Formatted 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 by ethnicity. Carriers of the KIR2DS2/KIR2DL2 genotype [KIR2DS2+/KIR2DL2+ versus KIR2DS2-/KIR2DL2+/- and KIR2DS2+/-/KIR2DL2-; odds ratio (OR) 2.51, P = 0.002] were overrepresented. In addition, frequency of the high-binding affinity FCGR3a-V/V158 genotype (VV versus VF/FF; OR = 3.05, P = 0.007) was increased, whereas that of the FCGR3a-F158 allele was reduced (OR = 2.58, P = 0.00 002). 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.
Keyword FC gamma receptor
Immune thrombocytopenia
Killer cell immunoglobulin-like receptors
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ
Additional Notes © 2011 Wolters Kluwer Health | Lippincott Williams & Wilkins.

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2012 Collection
School of Medicine Publications
 
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