Genetic Factors Associated With Opioid Therapy and Opioid Addiction

Ethnic Aspects of Valproic Acid P-Oxidation

“…This isoenzyme is highly expressed in the liver and to a certain extent in extrahepatic tissues, such as the brain, kidneys, digestive tract, and lungs [75,76] (Figure 5). The expression of CYP2B6 varies greatly among different ethnic groups due to non-genetic factors, SNVs, inducibility, and irreversible inhibition by various endogenous and exogenous compounds [77]. CYP2B6 accounts for up to 10% of functional CYP isoenzymes in the liver [76].…”

“…CYP2B6 is known to be an active catalyst for the formation of 4-ene-VPA, 4-OH-VPA, and 5-OH-VPA [72], which have both therapeutic and (mainly) toxic effects. In addition to VPA, CYP2B6 is involved in the metabolism of bupropion, cyclophosphamide, efavirenz, ifosfamide, ketamine, and methadone [75,77].…”

“…The human CYP2B6 gene is located on chromosome 19 at position 19q13.2 (OMIM 123930) and is highly polymorphic [79]. The CYP2B6*2 allelic variant is more common in Europe and Africa compared to Asian populations [77], and the CYP2B6*4 variant is more common in Africans, Americans, and Asians compared to European populations. Also, there is intraethnic and interethnic variability in the frequency of low-functional allelic variants of CYP2B6*6 and CYP2B6*18.…”

“…Also, there is intraethnic and interethnic variability in the frequency of low-functional allelic variants of CYP2B6*6 and CYP2B6*18. Thus, the allelic frequency of CYP2B6*6 ranges from 0.33 to 0.5 in African Americans and Africans, 0.10-0.21 in Asians, 0.14-0.27 in Caucasians, and 0.62 in residents of Papua New Guinea [77], although the allelic frequency may have intraethnic differences within a particular racial/ethnic group [77]. For example, the frequency of the CYP2B6*6 variant in the Nigerian Yoruba population is 42%, Kenya Kikuyu 34%, and Tswana Bostwana 22% [77].…”

“…Thus, the allelic frequency of CYP2B6*6 ranges from 0.33 to 0.5 in African Americans and Africans, 0.10-0.21 in Asians, 0.14-0.27 in Caucasians, and 0.62 in residents of Papua New Guinea [77], although the allelic frequency may have intraethnic differences within a particular racial/ethnic group [77]. For example, the frequency of the CYP2B6*6 variant in the Nigerian Yoruba population is 42%, Kenya Kikuyu 34%, and Tswana Bostwana 22% [77]. Additionally, the allelic frequency of CYP2B6*9 has been reported to be 55% in Congolese, 20% in South African Xhosa, and 37% in Cameroonian populations [77].…”