CYP2D6 gene polymorphism and enzyme activity in African Americans in southern California

Despite its importance in drug metabolism and disease susceptibility, CYP2D6 activity and genetic polymorphism have rarely been investigated in African American populations. In order to bridge this information gap, we examined the genotype and phenotype of the enzyme in 154 African American (AA) and 143 Caucasian (C) normal volunteers. As shown in Table 1, AAs are significantly more likely to possess*17 and*5, but less likely to have*4. Overall, the two groups were similar in their CYP2D6 activity as measured with the dextromethorphan as the probe (MR: 2.21±.78 for AAs; 2.11±.86 for Cs; t=1.02, NS). Two of 4 AAs and 6 of 7 Cs were classified as poor metabolizers (PMs) have two nonfunctioning alleles. CYP2D6 activity is determined by*17,*4*5 and age in AAs (R²=.33, F=18.8, p<.001) and by*4 and*XN Cs (R²=.14, F=10.8, p<.001). These results support previous findings of the importance of*17 in determining CYP2D6 activity in AAs. Table 1 Frequency of Key CYP2D6 Alleles in AAs and Cs %Alleles*2*3*4*5*10*17*NX AA 26.9 0.3 7.8 6.2 7.5 14.6 1.9 C 26.2 1.4 19.9 2.1 8.0 0.3 1.4.