Influence of CYP2D6 Deletion, Multiplication,-1584C~G, 31G~A and 2988G~A Gene Polymorphisms on Dextromethorphan Metabolism among Mexican Tepehuanos and Mestizos

Abstract

Theaim ofthisstudywastoexplain the variabil ityofCYP2D6 activity by the identification of CYP2D6 deletion and multiplications,and the single-nucleotidepolymorphisms(SNPs) -1584C---G, 31G---A and 298 8G -+A in Mexican Mestizo and Tepehuano subjects. One hundred twelve Mestizos and 99 Tepehuano Amerindians were studied, who were previously phenotyped with dextromethorphan. The frequencies of CYP2D6*2A [-1584C-+G] and *35 [-1584C-+G, 3 1G-+ A] were 10.7 and 4.1%, respectively, in Mestizos, which is evidently a trend towards an extensive metabolism in carriers of the -1584G change.In Tepehuanos, *2A wasidentified with afrequency of 20%, and the allele *35 was not found. The frequ encies of CYP206*5 (deletion)and *41[2988 G---Ai were 1.3 and 2.2%inMestizosand0.5and 1%inTepehuanos,respectively. The SNP 2988A was found to be significantly related with the intermediate metabolizer ph enotype in Mestizos (R =: 0.309; n =: 88; p =: 0.006).The multiplicationshad frequencies of4.1%inMestizosand 1.5%inTepehuanos. Only in theMestizos did thepresence ofmultiplicationssignificantly decrease the DM/DX (dextromethorphan/dextrorphan) values (R =: 0.273; n =: 88; p =: 0.016). The polymerphi smsstudied had different frequenciesbetween Tep ehuanosandMestizos(p <0.001); however,in theTepehuano group thesehad a lowinfluenceontheir phenotypicexpression.Ithelpstounderstand thegenotype-phenotyperelationshipsofCYP2D6in ourstudied populations.