A novel ABCC6 haplotype is associated with azathioprine drug response in myasthenia gravis.
Pharmacogenet Genomics
; 27(2): 51-56, 2017 02.
Article
en En
| MEDLINE
| ID: mdl-27922550
ABSTRACT
OBJECTIVE:
We investigated the association of single nucleotide polymorphisms (SNPs) in drug-metabolizing enzymes and transporters (DMETs) with the response to azathioprine (AZA) in patients affected by myasthenia gravis (MG) to determine possible genotype-phenotype correlations. PATIENTS ANDMETHODS:
Genomic DNA from 180 AZA-treated MG patients was screened through the Affymetrix DMET platform, which characterizes 1931 SNPs in 225 genes. The significant SNPs, identified to be involved in AZA response, were subsequently validated by allelic discrimination and direct sequencing. SNP analysis was carried out using the SNPassoc R package and the haploblocks were determined using haploview software.RESULTS:
We studied 127 patients in the discovery phase and 53 patients in the validation phase. We showed that two SNPs (rs8058694 and rs8058696) found in ATP-binding cassette subfamily C member 6, a subfamily member of ATP-binding cassette genes, constituted a new haplotype associated with AZA response in MG patients in the discovery cohort (P=0.011; odds ratio 0.40; 95% confidence interval 0.20-0.83) and in the combined cohort (P=0.04; odds ratio 1.58).CONCLUSION:
These findings highlight the role that the ATP-binding cassette subfamily C member 6 haplotype may play in AZA drug response. In view of the significant effects and AZA intolerance, these novel SNPs should be taken into consideration in pharmacogenetic profiling for AZA.
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Azatioprina
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Polimorfismo de Nucleótido Simple
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Proteínas Asociadas a Resistencia a Múltiples Medicamentos
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Estudios de Asociación Genética
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Miastenia Gravis
Tipo de estudio:
Prognostic_studies
/
Risk_factors_studies
Límite:
Adult
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Aged
/
Female
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Humans
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Male
/
Middle aged
Idioma:
En
Revista:
Pharmacogenet Genomics
Asunto de la revista:
FARMACOLOGIA
/
GENETICA MEDICA
Año:
2017
Tipo del documento:
Article
País de afiliación:
Italia