Case-control study of the association between select HLA genes and anti-erythropoietin antibody-positive pure red-cell aplasia.
Pharmacogenomics
; 9(2): 157-67, 2008 Feb.
Article
em En
| MEDLINE
| ID: mdl-18370845
ABSTRACT
AIMS:
Antibody (Ab)-positive pure red-cell aplasia (PRCA) is a very rare but serious adverse event associated with recombinant human erythropoietin treatment (4.1 reports per 100,000 patient-years) in which patients produce antibodies to recombinant and endogenous erythropoietin, halting red blood cell production. In a previous case series, four Thai subjects with chronic kidney disease and Ab-positive PRCA were reported to have the HLA-DRB1*9 allele. To confirm a possible association of HLA-DRB1*9 and Ab-positive PRCA, we performed a pharmacogenomic analysis using subjects from an earlier case-control study of risk factors associated with Ab-positive PRCA, which had been performed using subjects from Europe or Canada. The primary goal of the analysis was to test the association between HLA-DRB1*9 and Ab-positive PRCA. A secondary goal was to perform an exploratory analysis in order to identify additional HLA alleles potentially associated with Ab-positive PRCA. PATIENTS &METHODS:
Subjects were taken from a case-control study of Ab-positive PRCA in chronic kidney disease patients treated in Europe or Canada. Ab-positive PRCA cases (n=24) were matched to controls (n=81) by timing of treatment exposure and, when possible, by location.RESULTS:
The allele frequency of HLA-DRB1*9 was 12.5% in cases vs 1.2% in controls (p=0.002). The frequency of the HLA-DRB1*9/other genotype was 25.0% in cases vs 2.5% in controls (p=0.004; OR 10.8 [95% CI 2.2-53.7]). Within the exploratory analysis, six additional HLA alleles (HLA-A*25, HLA-B*53, HLA-C*12, HLA-DQB1*3, HLA-DQB1*6 and HLA-DRB1*4) were also found to be associated with Ab-positive PRCA.CONCLUSION:
This study confirmed that HLA-DRB1*9 occurs at a significantly higher frequency in Ab-positive PRCA cases than in controls; however, within this sample set, carrying the *9 allele was neither necessary nor sufficient to cause Ab-positive PRCA.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Autoanticorpos
/
Eritropoetina
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Aplasia Pura de Série Vermelha
/
Antígenos HLA
Tipo de estudo:
Etiology_studies
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Observational_studies
/
Prognostic_studies
Limite:
Adult
/
Aged
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Female
/
Humans
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Male
/
Middle aged
Idioma:
En
Ano de publicação:
2008
Tipo de documento:
Article