Original ArticlesEvidence for environmental influence on CYP2D6-catalysed debrisoquine hydroxylation as demonstrated by phenotyping and genotyping of Ethiopians living in Ethiopia or in SwedenAklillu, Eleni; Herrlin, Karin; Gustafsson, Lars L; Bertilsson, Leif; Ingelman-Sundberg, MagnusAuthor Information aDivision of Molecular Toxicology, IMM, Karolinska Institutet and bDivision of Clinical Pharmacology, Department of Laboratory Sciences and Technology at Karolinska Institutet, Huddinge University Hospital, Stockholm, Sweden Tel: +468 728 7735; fax: +468 337 327; e-mail: [email protected] Correspondence to Dr Magnus Ingelman-Sundberg, Division of Molecular Toxicology, IMM, Box 210, Karolinska Institutet, SE-171 77 Stockholm, Sweden Received 21 February 2002 Accepted 22 April 2002 Pharmacogenetics: July 2002 - Volume 12 - Issue 5 - p 375-383 Buy Abstract Black Africans show lower rates of CYP2D6- and CYP2C19-dependent drug metabolism compared to Caucasians of the same apparent genotype. To determine if environmental factors are responsible for this difference, the genotypes and phenotypes of CYP2D6 and CYP2C19 among Ethiopians living in Sweden (n= 70) were assessed and compared to our previously published data from Ethiopians living in Ethiopia (n= 114) and Swedish Caucasians (n= 134). There was no significant difference inCYP2C19genotype or phenotype as assessed by mephenytoin between Ethiopians in Sweden or in Ethiopia. However, Swedes were significantly more rapid for CYP2C19 activity than both Ethiopian groups (P< 0.01). A comparison of the debrisoquine MR among individuals of the sameCYP2D6genotype revealed that Swedes exhibited the highest rate of debrisoquine metabolism, followed by Ethiopians in Sweden and Ethiopians in Ethiopia. The difference between the Ethiopian groups was significant (P< 0.02 using a univariate test ANOVA) and amounted to approximately 50% of the magnitude of the MR difference between Swedes and Ethiopians in Ethiopia. It is tempting to speculate that inhibitory dietary factors may explain the differences seen between the two Ethiopian groups and that these components in the past might have contributed to dietary stress-mediated selection of duplicated and multiduplicated activeCYP2D6genes, as frequently seen in Ethiopians. In conclusion, the results indicate a significant influence of environmental factors as an explanation for the difference in capacity for CYP2D6, but not CYP2C19 metabolism between Caucasians and Black Africans. Additional factors remain to be elucidated to fully explain the interethnic differences in CYP2D6 activity. © 2002 Lippincott Williams & Wilkins, Inc.