Pharmacogenetics Therapeutic Response

MDR1 Expression Predicts Outcome of Liver Transplantation 

The investigators measured messenger ribonucleic acid (mRNA) expression levels of MDRl and CYP3A4 in mucosal cells of the upper jejunum collected during living-donor liver transplantation in 48 recipients. Tacrolimus was initiated at an oral dose of 0.075 mg/kg every 12 hours and adjusted on the basis of trough levels in whole blood. 

SNPs Predispose to Cancer and Alter Response to Therapy 

Alteration of a single nucleotide in a gene can determine whether the gene will predispose an individual to developing cancer. At the same time these SNPs can alter gene function in ways that affect response to therapy or chemoprophylaxis. 

The investigators found that the described 10 SNP variants of SRD5A2 differ in their biologic effects, not only in how much they affect levels of DHT, but also in their response to finasteride, a competitive inhibitor of 2,5-alpha reductase. Finasteride (Proscar) is marketed for the treatment of BPH and is under investigation for the chemoprevention of prostate cancer. The investigators found a 200-fold range in activity of the enzymes encoded by these gene variants and as much as a 60-fold difference in the ability of finasteride to inhibit the enzyme s activity. 

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Suzuki A, Mihara K, Kondo T, et al. The relationship between dopamine D2 receptor polymorphism at the TaqlA locus and therapeutic response to nemonapride, a selective dopamine antagonist, in schizophrenic patients. Pharmacogenetics 2000 l0f4) 335 41. 

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