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It’s simple really: you have superfamilies of proteins within which there are families within which there are members, and a member may have several, quite different, names. The transporter protein that concerns us here belongs to the ATP binding cassette superfamily of multidrug transporters; more specifically it is a member of subfamily B, in fact member one. So it is the ATP binding cassette subfamily B member 1 transporter (ABCB1 transporter). But you could, if you wanted to, call it MDR1 or P-glycoprotein 170. (Let’s stick with ABCB1 for now, shall we?) It is a transmembrane glycoprotein that controls entry of lipophilic molecules (including at least four antiepileptic drugs) into the brain by acting as a drug efflux pump, and it may be part of the blood-brain barrier. Up-regulation of ABCB1 is associated with drug resistance in cancer, rheumatoid arthritis, and inflammatory bowel disease. ABCB1 concentrations are increased in brain lesions causing epilepsy, and many antiepileptic drugs are lipophilic. Now research on patients in London (
) has shown that a particular genotype of an ABCB1 gene polymorphism is found more often in patients with drug resistant than with drug responsive epilepsy.
The ABCB1 C3435T polymorphism was genotyped (CC, CT, or TT) for 200 patients with drug resistant epilepsy, 115 with drug responsive epilepsy, and 200 controls (neurological patients without epilepsy. (The age distribution is not stated but they were presumably mainly, if not all, adults.) The genotype distribution (CC; CT; TT) was 27.5%; 53%; 19.5% in the patients with drug resistant epilepsy, 15.7%; 54.8%; 29.6% in the drug sensitive group, and 18.5%, 58%, 23.5% in the controls. Patients with drug resistant epilepsy were 2.7 times more likely to have the CC rather than the TT genotype than were patients with drug sensitive epilepsy. The researchers argue that the polymorphism itself, because it is silent (does not alter the amino acid sequence), is unlikely to be the cause of multidrug resistance but is more likely to be associated with another variant which is the cause.
Changes in transporter protein genes may be associated with resistance to antiepileptic drugs.
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