Analysis of the 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 gap, we examined the genotype and phenotype of the enzyme in 154 African-American (AA) and 143 Caucasian (C) normal volunteers. 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 dextromethorphan as the probe (metabolic ratio 2.21 +/- 0.78 for AAs; 2.11 +/- 0.86 for Cs; t = 1.02, NS). Two of four AAs and six of seven Cs were classified as poor metabolizers and have two nonfunctioning alleles. CYP2D6 activity is determined by *17, *4, *5 and age in AAs (r2 = 0.33, f = 18.8, P < 0.001) and by *4 and *XN in Cs (r2 = 0.14, f = 10.8, P < 0.001). These results support previous findings demonstrating the importance of *17 in determining CYP2D6 activity in AAs.
Wan
Y J
YJ
Department of Pathology, Harbor-UCLA Medical Center, Torrance, CA, USA.
Poland
R E
RE
Han
G
G
Konishi
T
T
Zheng
Y P
YP
Berman
N
N
Lin
K M
KM
D000328:Adult; D001741:Black or African American; D000367:Age Factors; D000483:Alleles; D044383:Black People / Q000235:genetics*; D002140:California; D019389:Cytochrome P-450 CYP2D6 / Q000235:genetics*; D003915:Dextromethorphan / Q000378:metabolism*; D005260:Female; D020440:Gene Duplication; D005787:Gene Frequency; D006801:Humans; D008297:Male; D011110:Polymorphism, Genetic; D012737:Sex Factors; D044465:White People / Q000235:genetics
D003915:Dextromethorphan; D019389:Cytochrome P-450 CYP2D6