title: Genetic polymorphisms affect efficacy and adverse drug reactions of DMARDs in rheumatoid arthritis.
abstract: Disease-modifying antirheumatic drugs (DMARDs) and biological agents are critical in preventing the severe complications of rheumatoid arthritis (RA). However, the outcome of treatment with these drugs in RA patients is quite variable and unpredictable. Drug-metabolizing enzymes (dihydrofolate reductase, cytochrome P450 enzymes, N-acetyltransferases, etc.), drug transporters (ATP-binding cassette transporters), and drug targets (tumor necrosis factor-α receptors) are coded for by variant alleles. These gene polymorphisms may influence the pharmacokinetics, pharmacodynamics, and side effects of medicines. The cause for differences in efficacy and adverse drug reactions may be genetic variation in drug metabolism among individuals. Polymorphisms in drug transporter genes may change the distribution and excretion of medicines, and the sensitivity of the targets to drugs is strongly influenced by genetic variations. In this article, we review the genetic polymorphisms that affect the efficacy of DMARDs or the occurrence of adverse drug reactions associated with DMARDs in RA.
authors.affiliation: aKey Lab of Dermatology, Ministry of Education, Key Lab of Gene Resource Utilization for Severe Genetic Disorder, Anhui Province bInstitute of Clinical Pharmacology, Anhui Medical University, Key Laboratory of Anti-inflammatory and Immunopharmacology of Education Ministry of China, Hefei, Anhui, China.
authors.forename: Ling Ling
authors.initials: LL
authors.lastname: Zhang
authors.forename: Sen
authors.initials: S
authors.lastname: Yang
authors.forename: Wei
authors.initials: W
authors.lastname: Wei
authors.forename: Xue Jun
authors.initials: XJ
authors.lastname: Zhang
mesh_terms: D000483:Alleles; D018501:Antirheumatic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy*; D001191:Arylamine N-Acetyltransferase / Q000235:genetics; D053264:B-Cell Activating Factor / Q000235:genetics; D003580:Cytochromes / Q000235:genetics; D006801:Humans; D015850:Interleukin-6 / Q000235:genetics; D008780:Methyltransferases / Q000378:metabolism; D011110:Polymorphism, Genetic; D012460:Sulfasalazine / Q000009:adverse effects / Q000627:therapeutic use; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics
chemical_list: D018501:Antirheumatic Agents; D053264:B-Cell Activating Factor; D003580:Cytochromes; D015850:Interleukin-6; C505719:TNFSF13B protein, human; D014409:Tumor Necrosis Factor-alpha; D012460:Sulfasalazine; D008780:Methyltransferases; C022745:thiopurine methyltransferase; D001191:Arylamine N-Acetyltransferase; C478900:NAT2 protein, human