Farmacogenética del "CYP2D6" en la población argentina general y judía Ashkenazi

Zusammenfassung

Introduction Interethnic variability of CYP2D6 allelic variants distribution and frequencies has been showed in numerous populations. This information might be relevant to improve pharmacological therapies by increasing efficacy and decreasing adverse side effects. Argentinean population has a multiethnic origin and there are very few studies of genotypic and allelic frequencies of CYP2D6 gene or either among Argentinean ethnic groups. Objective The aim of this study was to determine interethnic variability of CYP2D6 polymorphism in two Argentinean subpopulations, one of multiethnic origin and other referred with Jewish Ashkenazi ancestry. Additionally to compare these frequencies with those reported in other populations with similar ethnic origin: Ibero-American and Jewish Ashkenazi populations. Material and methods Nine CYP2D6 allelic variants and copy numbers were studied in two samples of different groups of Argentinean population. The sample was constituted by 419 healthy, no related, both sexes participants: 246 multiethnic (GA) and 173 self referred as Ashkenazi Jewish (JA). The CYP2D6 genotype was analyzed by PCR and PCR' restriction fragment length polymorphism for the CYP2D6 *3, *4, *5, *6, *10, *17, and multiplicated alleles. The relationship between CYP2D6 genotype and phenotype was evaluated assigning a value relative to each variant CYP2D6 allele based on the "activity score" system: Ultra rapid Metabolizers (URMs: more than two active CYP2D6 genes) and Poor Metabolizers (PMs: no active CYP2D6 genes). Results Significant differences were found in CYP2D6 polymorphism frequencies between both populations. A higher frequency of CYP2D6*41 genotypes carriers was found in JA population respect GA (p<0.05; 0.162 y 0.077, respectively) and of multiplicated alleles in JA population respect of GA (0.085 y 0.046, respectively), and a significant higher frequency of URMs (p<0.05) in JA population (0.115) respect to GA population (0.065). The frequency of URMs in GA population was similar to that described in the Caucasian population of Ibero-America and PMs frequency was lower that described in Spanish population. However, Ashkenazi Jewish population from Argentina showed the higher frequency of CYP2D6*41 and the higher percentage of URMs of all Ibero-American population. In contrast, no significant differences were found in the genotypic, allelic or metabolic phenotype among JA population and other Jewish Ashkenazi populations. Discussion and Conclusions The results of this study show that there are interethnic differences in CYP2D6 genetic polymorphisms frequencies between both Argentinean subpopulations. Among the results it should be noted that Argentinean Jewish Ashkenazi has a very high frequency of CYP2D6*41 allele, higher than GA population and other in Ibero-American populations; and a higher URMs frequency n GA population and the higher of all Ibero-American populations. Additionally, the frequency of CYP2D6 genetic polymorphism in both Argentinean populations studied, multiethnic and Jewish Ashkenazi origin, are similar to other populations with similar ethnic origin, multiethnic and Jewish. In conclusion, to ascertain the ethnic origin in Argentinean patients might have clinical utility, because JA individuals may need special recommendations in drug prescription, different to those recommended for patients of multiethnic origin.