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 present study analyzed the mRNA expression levels of genes involved in the transport and metabolism of methotrexate (MTX) (RFC1,
ABCC1
, ABCB1, GGH, FPGS,
ATIC
, TS, MTHFR, MTRR, MS and MTHFD1) in patients with acute leukemia (AL). The expression levels of the examined genes were analyzed by reverse transcription quantitative polymerase chain reaction (RT-qPCR) in patients with AL (ALL:50/AML:19) and 66 healthy individuals. The mRNA expression levels of RFC1, MS, MTRR, MTHFR and ABCB1 were decreased (P<0.05), while those of GGH, FPGS, TS and MTHFD1 (P<0.05) were overexpressed in patients with AL. Patients with high mRNA levels of GGH (OR=4.28, 95% CI=1.29-14.14), TS (OR=7.14, 95% CI 1.84-27.81), MTHFR (OR=4.81, 95% CI=1.31-17.64), ABCB1 (OR=4.61, 95% CI=1.33-15.97) and
ABCC1
(OR=5.50, 95% CI=1.12-27.06) had a higher chance of relapse. Interestingly, high mRNA levels of RFC1 are a protective factor in the risk of AL relapse (OR=0.22, 95% 0.06-0.80). The results of the present study indicated that deregulation of folate pathway gene expression is associated with poor prognosis in AL and that the expression levels of these markers could serve as novel molecular targets for the treatment of patients with AL.
...
PMID:Deregulation of folate pathway gene expression correlates with poor prognosis in acute leukemia. 3145 89
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
