Polymorphism of CYP2D6 in Black populations: implications for psychopharmacology

L. DiAnne Bradford, Ward G. Kirlin
1998 International Journal of Neuropsychopharmacology  
Drug-metabolizing enzymes found primarily in the liver (CYP450) are a major determinant of therapeutic drug response. Polymorphism dependent upon race\ethnic origin for CYP2D6 is now well-established. Despite consistent reports of ethnic differences in pharmacologic response to antidepressants and neuroleptics, there is a paucity of data on controlled clinical trials and studies determining polymorphic characteristics of CYP2D6 enzymes in African-Americans. There is little and conflicting
more » ... d conflicting information available on black populations (Africans, bushmen, Australian Aborigines or African Americans). The prevalence of poor metabolizers in Black populations has been estimated from 0 to 19 %, compared with consistent reports of poor metabolizer status in Caucasians (5-10 %) and Asians (0-2 %). Within the extensive metabolizer category, Asians have higher metabolic ratios (that is, slower metabolism) than Caucasian extensive metabolizers. A high frequency of a mutant gene, CYP2D6*10 has been associated with the slower metabolic rate in Asians. Previous research suggests that slower metabolic rates compared with Caucasians may also be characteristic of Black populations. Recent reports suggest that a novel gene mutant in Black populations, CYP2D6*17, associated with a slower metabolic rate, may occur in a high frequency in these populations. Common clinical practice, supported by controlled clinical studies in Asians, have led to a reduction in dosage recommendations for many antidepressants and neuroleptics for this ethnic group. It is imperative that the determinants of bioavailability be established in African-Americans in order to establish rational drug therapy guidelines for this population. Most drugs are taken orally and metabolized in the liver by cytochrome P-450 (CYP450) enzymes. Although over 20 families have been identified thus far, the CYP1A, 2C, 2D, 2E, and 3A are involved in the metabolism of most drugs in common clinical use (Meyer, 1996) . Numerous factors, including genetics, affect drug metabolism and thus alter the bioavailability of therapeutic drugs. The rate of metabolism by several of the CYP450 enzyme subfamilies varies, due to genetically-determined polymorphisms in all populations studied. These metabolic polymorphisms are determined by gender, for example, CYP1A2 (Relling et al., 1992 ; see Harris et al., 1995 for review) and racial\ethnic origin, for example, CYP1A1, CYP2D6, CYP2C19 (Bertilsson, 1995) . Recent research using phenotyping and genotyping techniques has reflec-
doi:10.1017/s1461145798001187 pmid:11281961 fatcat:y3xeiq663jh4lkpoxyrddjpjjy