Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.6.3.44 (P-glycoprotein)
 13,344 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Resistance to glucocorticoids (GCs) remains a tricky problem complicating the therapy of ITP. Recently, ATP binding cassette gene B1 gene (ABCB1) was reported to be correlated with susceptibility and therapeutic efficacy of autoimmune diseases through P-glycoprotein (Pgp). We investigated three single nucleotide polymorphisms (SNPs) of ABCB1 and their haplotypes by PCR-RFLP (restriction fragment length polymorphism) method in 471 ITP patients and 383 healthy controls, patients were further assigned into GCs-responsive and -non-responsive group according to the therapeutic effects of GCs. We observed a remarkable difference in genotypes of G2677T/A between GCs-responsive and non-responsive group, but not between patients and controls. A frequently expression of T/A allele within G2677T/A was recorded in GCs-responsive group. Furthermore, we found that some haplotypes (CGC, CTC/CAC, CTT/CAT, TGC, TGT, TTC/TAC and TTT/TAT, in the order of position 1236-2677-3435) were presented significantly differences between non-responsive and responsive group. No difference of C1236T and C3435T polymorphisms was observed between ITP and controls, and between the GCs-responsive and -non-responsive group. Our findings suggest that ABCB1 polymorphisms, as well as haplotypes derived from C1235T, G2677T/A and C3435T, are associated with inter-individual differences of GCs treatment in ITP.
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PMID:Association of ABCB1 gene polymorphisms and haplotypes with therapeutic efficacy of glucocorticoids in Chinese patients with immune thrombocytopenia. 2448 77

Imatinib mesylate (IM) has so far been the standard of care for treating chronic myeloid leukemia (CML), but the initial striking efficacy of this drug has been overshadowed by the development of clinical resistance, which may in part be caused by pharmacogenetic variability. The ATP-binding cassette, subfamily B, member 1 (ABCB1) gene codes for P-glycoprotein (P-gp), a membrane-bound efflux transporter known to affect the pharmacokinetics of many drugs. IM is a substrate of the P-gp-mediated efflux. ABCB1 single nucleotide polymorphisms (SNPs) have been reported as modulators of ABCB1-mediated transport, affecting IM's bioavailability and consequently the treatment outcome of IM therapy. We aimed to examine the association between ABCB1 SNPs and the likelihood of achieving optimal response in IM-treated CML patients. Three ABCB1 SNPs (C1236T, G2677T, and C3435T) were genotyped in 100 Egyptian patients with CML undergoing IM therapy using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay. The optimal response rate did not differ significantly between C1236T, G2677T, or C3435T genotypes (P > 0.05). Optimal response rate was significantly different among patients with the CGC, TTT, TGC, CGT, TGT, CTC, CTT, and TTC haplotypes (P = 0.023). The 1236T-2677G-3435T haplotype was significantly associated with lower probability of achieving optimal response (P = 0.001). ABCB1 SNPs haplotype analysis should be taken into account in an attempt to get clearer insights into who is likely to respond optimally to IM for identifying CML patients who may not respond optimally to standard-dose IM therapy and potentially need an individualized therapeutic approach.
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PMID:ABCB1 haplotypes but not individual SNPs predict for optimal response/failure in Egyptian patients with chronic-phase chronic myeloid leukemia receiving imatinib mesylate. 2530 Nov 12