The African‐specific CYP2D6*17 allele encodes an enzyme with changed substrate specificity

Abstract

We found differences in the disposition of 4 CYP2D6 probe drugs in black Tanzanians compared with Swedes. The differences were caused by the presence of CYP2D6.17 and CYP2D6.29. The results show that CYP2D6.17 exhibits altered substrate specificity compared with CYP2D6.1 and CYP2D6.2.

A Physiologic Approach to the Pharmacogenomics of Hypertension

“…Indeed, the emphasis of this review has been on drug efficacy and agent selection. However, there is significant evidence supporting variants predicting adverse events including the hyperuricemia of thiazide use 94 , bradycardia associated with β-blockers [5][6][7][8]95,96 , and ACEI-related cough 97 .…”

CYP2D6 genetic variation in healthy adults and psychiatric African-American subjects: implications for clinical practice and genetic testing

“…This may be one reason why variations in probe substrate metabolic ratios differ so markedly in African-Americans. 33 The concept of allele substrate-dependent versus allele global depression in CYP2D6 function is easiest to visualize from the CYP2D6*17 allele perspective. The CYP2D6*17 allele has generally been characterized as an allele with diminished CYP2D6 activity, 24,25,[34][35][36] but there is some evidence that this classification is wrong.…”

“…The CYP2D6*17 allele has generally been characterized as an allele with diminished CYP2D6 activity, 24,25,[34][35][36] but there is some evidence that this classification is wrong. 35,33 The psychiatric patients evaluated in this study came from a larger group of patients prescribed risperidone in which the risperidone and 9-OH risperidone levels were determined. 37 The risperidone/9-OH ratio in patient plasma is dependent on CYP2D6 activity as 9-OH risperidone is formed by CYP2D6 metabolism of risperidone.…”

Analysis of CYP2C9*5 in Caucasian, Oriental and Black-African populations

“…Genomic DNA samples used in the present study were from 200 Caucasians from Sweden, 150 Orientals from Korea, 150 Ethiopians and 183 black Tanzanians, all previously genotyped for other CYP polymorphisms [4,7,23,24,25,26,27]. The subjects were unrelated and healthy.…”