The MDR1/ABCB1 gene, a high-impact risk factor for cardiac transplant rejection.
Transplantation
; 82(12): 1677-82, 2006 Dec 27.
Article
em En
| MEDLINE
| ID: mdl-17198259
ABSTRACT
BACKGROUND:
Variations in the expression and activity levels of the multidrug-resistance MDR1/ABCB1 encoded P- glycoprotein (P-gp) have an impact on the therapeutic efficacy of many drugs. C3435T and G2677 polymorphisms of the MDR1/ABCB1 gene correlate with cellular expression levels of P-gp, a membrane-bound efflux pump which removes a multitude of drugs, including chemotherapy drugs and immunosuppressants, from cells. We aimed to investigate whether the phenomenon of drug resistance, mediated by the MDR1/ABCB1 gene and seen in tumor cells to chemotherapeutic agents, is important in the field of transplantation, predisposing some patients to resistance to immunosuppressants.METHODS:
G2677 and C3435T polymorphisms of the ABCB1 gene were determined by PCR in 170 heart transplant recipients. We examined the relationship between MDR1/ABCB1 polymorphisms and endomyocardial biopsy-proven rejection (EBPR) determined by biopsy performed at set intervals according to a standard protocol.RESULTS:
A significant relationship was found between a patient's C3435T genotype and freedom from first grade > or =3A rejection episode. 3435-CC recipients were 1.8 times (1.05-3.09; P = 0.03) more likely to undergo a > or =3A rejection episode in the first 12 months. Haplotypes derived from the G2677 and C3435T polymorphisms (GG/CC, GT/CT and TT/TT) amplified this phenomenon further (log rank, P = 0.03; HR 2.18; 1.21-4.26; P = 0.02).CONCLUSIONS:
ABCB1 polymorphisms correlate with freedom from grade > or =3A EBPR and we believe that this may be attributed to MDR1/ABCB1 encoded P-gp mediating the efflux of immunosuppressants out of leukocytes, with depleted immunosuppressant levels in leukocytes manifesting as increased cellular rejection.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Polimorfismo Genético
/
Transplante de Coração
/
Membro 1 da Subfamília B de Cassetes de Ligação de ATP
/
Transportadores de Ânions Orgânicos
/
Rejeição de Enxerto
Tipo de estudo:
Etiology_studies
/
Guideline
/
Risk_factors_studies
Limite:
Adult
/
Female
/
Humans
/
Male
/
Middle aged
Idioma:
En
Revista:
Transplantation
Ano de publicação:
2006
Tipo de documento:
Article
País de afiliação:
Reino Unido