Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: UNIPROT:P33527 (
ABCC1
)
1,164
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
The ATP-binding cassette (ABC) transporter family is a large class of ATP energy-dependent transmembrane proteins, and its primary function is to use the energy produced by ATP hydrolysis to transfer the substrate bound to the plasma membrane. This family is also closely related to multidrug resistance (MDR) in various diseases. Among the ABC transporter proteins, P-glycoprotein (P-gp),
multidrug resistance-associated protein (MRP)
and breast cancer resistance protein (BCRP) are the main members associated with MDR. At present, the roles of these transporters in therapeutic failures have been extensively studied and reviewed in cancer; however, they have rarely been described in autoimmune diseases (AIDs).
AID
is a group of chronic inflammatory diseases of unknown aetiology.
AID
's basic feature is the production of a large number of autoantibodies, which leads to extensive damage to multiple systems and multiple organs. Disease-modifying anti-rheumatic drugs (DMARDs) are commonly used in the treatment of
AID
, but a considerable number of patients have no response or develop resistance to these drugs over time. This phenomenon may be related to the abnormal expression of the ABC transporter, which leads to a decrease in the amount of drug entering cells that produce MDR. This article reviews the effects of DMARDs on the expression and function of P-gp, MRPs, and BCRP and the related molecular mechanism in the treatment of
AID
.
...
PMID:The effects of DMARDs on the expression and function of P-gp, MRPs, BCRP in the treatment of autoimmune diseases. 3002 80
Rheumatoid arthritis (RA) is a chronic systemic
autoimmune disease
that causes loss of joint function and significantly reduces quality of life. Plasma metabolite concentrations of disease-modifying anti-rheumatic drugs (DMARDs) can influence treatment efficacy and toxicity. This study explored the relationship between DMARD-metabolising gene variants and plasma metabolite levels in RA patients. DMARD metabolite concentrations were determined by tandem mass-spectrometry in plasma samples from 100 RA patients with actively flaring disease collected at two intervals. Taqman probes were used to discriminate single-nucleotide polymorphism (SNP) genotypes in cohort genomic DNA: rs246240 (
ABCC1
), rs1476413 (
MTHFR
), rs2231142 (
ABCG2
), rs3740065 (
ABCC2
), rs4149081 (
SLCO1B1
), rs4846051 (
MTHFR
), rs10280623 (
ABCB1
), rs16853826 (
ATIC
), rs17421511 (
MTHFR
) and rs717620 (
ABCC2
). Mean plasma concentrations of methotrexate (MTX) and MTX-7-OH metabolites were higher (
p
< 0.05) at baseline in rs4149081 GA genotype patients. Patients with rs1476413 SNP TT or CT alleles have significantly higher (
p
< 0.001) plasma poly-glutamate metabolites at both study time points and correspondingly elevated disease activity scores. Patients with the rs17421511 SNP AA allele reported significantly lower pain scores (
p
< 0.05) at both study intervals. Genotyping strategies could help prioritise treatments to RA patients most likely to gain clinical benefit whilst minimizing toxicity.
...
PMID:Clinical and Laboratory Associations with Methotrexate Metabolism Gene Polymorphisms in Rheumatoid Arthritis. 3299 83
