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)
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
