The KIR2DS2/DL2 genotype is associated with adult persistent/chronic and relapsed immune thrombocytopenia independently of FCGR3a-158 polymorphisms.
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.
Clinical Immunohaematology Laboratory, Queensland Institute of Medical Research, Brisbane, Queensland, Australia.
Jamie P
JP
Nourse
Rod
R
Lea
Pauline
P
Crooks
Gillian
G
Wright
Huyen
H
Tran
John
J
Catalano
Tim
T
Brighton
Andrew
A
Grigg
Paula
P
Marlton
Maher K
MK
Gandhi
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D002908:Chronic Disease; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D011446:Prospective Studies; D016553:Purpura, Thrombocytopenic, Idiopathic / Q000235:genetics* / Q000473:pathology; D017452:Receptors, IgG / Q000235:genetics*; D054340:Receptors, KIR / Q000235:genetics*; D054343:Receptors, KIR2DL2 / Q000235:genetics*; D012008:Recurrence; D055815:Young Adult
C496124:FCGR3A protein, human; C515077:KIR2DL2 protein, human; C433932:KIR2DS2 protein, human; D017452:Receptors, IgG; D054340:Receptors, KIR; D054343:Receptors, KIR2DL2