R Ismail1, A Hussein, L K Teh, M Nizam Isa. 1. Department of Pharmacology, Universiti Sains Malaysia, 16150 Kota Bharu, Kelantan, Malaysia. isrusli@kb.usm.my
Abstract
BACKGROUND: Although they originated from China, Malays have undergone a lot of intermarriages. A study suggested that CYP2D6 poor metabolism (PM) phenotype was more common in Malays compared to Chinese. CYP2D6 is highly polymorphic and is involved in the metabolism of many drugs and has been implicated in some environmentally-induced diseases. It is therefore useful to further study this polymorphism in Malays. OBJECTIVE: To study debrisoquine metabolism phenotypes in healthy Malay volunteers. METHOD: We administered debrisoquine to 51 Malays and used HPLC to measure urinary debrisoquine and 4-hydroxy debrisoquine to calculate debrisoquine metabolic ratios (MR). RESULTS: Debrisoquine MR varied widely and with probit analysis we were able to identify population subsets. Although the frequency distribution for the MR showed a right shift, the shift was less than that reported for the Chinese population. We also found 2 poor metabolizers and one ultra rapid metaboliser in the population. CONCLUSION: The genetic polymorphism of debrisoquine in Malays differs from that in the Chinese. Both their PM prevalence and their MR distribution suggest that they are intermediate between Europeans and Chinese in relation to this polymorphism. Studies to compare CYP2D6 genotypes between them and related races would be useful to further define these differences.
BACKGROUND: Although they originated from China, Malays have undergone a lot of intermarriages. A study suggested that CYP2D6 poor metabolism (PM) phenotype was more common in Malays compared to Chinese. CYP2D6 is highly polymorphic and is involved in the metabolism of many drugs and has been implicated in some environmentally-induced diseases. It is therefore useful to further study this polymorphism in Malays. OBJECTIVE: To study debrisoquine metabolism phenotypes in healthy Malay volunteers. METHOD: We administered debrisoquine to 51 Malays and used HPLC to measure urinary debrisoquine and 4-hydroxy debrisoquine to calculate debrisoquine metabolic ratios (MR). RESULTS:Debrisoquine MR varied widely and with probit analysis we were able to identify population subsets. Although the frequency distribution for the MR showed a right shift, the shift was less than that reported for the Chinese population. We also found 2 poor metabolizers and one ultra rapid metaboliser in the population. CONCLUSION: The genetic polymorphism of debrisoquine in Malays differs from that in the Chinese. Both their PM prevalence and their MR distribution suggest that they are intermediate between Europeans and Chinese in relation to this polymorphism. Studies to compare CYP2D6 genotypes between them and related races would be useful to further define these differences.
Authors: Mohammad Reza Shiran; Fatemeh Sarzare; Fatemeh Merat; Ebrahim Salehifar; Ali Akbar Moghadamnia; Seyed Mohammad Bagher Hashemi Soteh Journal: Caspian J Intern Med Date: 2011