Estudio del polimorfismo de CYP2D6 en población mestiza peruana
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Date
2024
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Universidad Nacional de Trujillo
Abstract
El gen citocromo P450 2D6 (CYP2D6) es altamente polimórfico que codifican enzimas que metabolizan más del 25 % de los fármacos de uso clínico; siendo CYP2D6*3 y CYP2D6*4 los polimorfismos más relevantes en Latinoamérica. La investigación tuvo por objetivo evaluar el polimorfismo de CYP2D6 en la población mestiza peruana. Este estudio es observacional descriptivo de corte transversal y con reclutamiento prospectivo, muestreo no probabilístico por conveniencia e inclusión consecutiva. La muestra estuvo constituida por 234 voluntarios mestizos peruanos (varones: n= 174; 74,36 %; mujeres: n = 60; 25,64 %) de ellos, 134 fueron residentes de Lima (57,26 %), 50 de Tacna (21,37 %), y 50 de Junín (21,37 %). Los alelos CYP2D6*3 (rs35742686, 2549A>del) y CYP2D6*4 (rs3892097, 1846G>A) se genotipó por PCR-Real Time con sondas TaqMan®; a partir de los genotipos se infirió los fenotipos metabolizadores. Se observó CYP2D6*3 y CYP2D6*4 con una frecuencia de 1,5 % (prueba ji cuadrado X2 0,0539; 1 grado de libertad; valor-p > 0,05) y 5,1 % (X2 3,46; 1 grado de libertad), respectivamente. Por estratificación de regiones se evidenció que los portadores CYP2D6*4 (X2 20,8263) de Junín no están en equilibrio de Hardy-Weinberg (HWE); sin embargo, al análisis global las frecuencias para ambos polimorfismos estuvieron en HWE (X2 <3,84). El 11,55 % de los sujetos se catalogaron como metabolizadores intermedios (CYP2D6*1/*3 o CYP2D6*1/*4) con una puntuación de actividad 0<X<1,25; y 0,85% como metabolizadores pobres (CYP2D6*4/*4). Se concluye que las frecuencias de los polimorfismos CYP2D6*3 y CYP2D6*4 son bajas y esperadas para la población mestiza peruana con ascendencia tricontinental y latinoamericana. Debido a los metabolizadores descritos, estos hallazgos son relevantes en la práctica clínica.
The cytochrome P450 2D6 (CYP2D6) gene is highly polymorphic that encodes enzymes that metabolize more than 25 % of drugs in clinical use; CYP2D6*3 and CYP2D6*4 being the most relevant polymorphisms in Latin America. The objective of the research was to evaluate the CYP2D6 polymorphism in the Peruvian mestizo population. This study is an observational, descriptive, cross-sectional study with prospective recruitment, non-probabilistic sampling for convenience and consecutive inclusion. The sample was made up of 234 Peruvian mestizo volunteers (men: n= 174; 74.36 %; women: n = 60; 25.64 %) of them, 134 were residents of Lima (57.26 %), 50 from Tacna (21.37 %), and 50 de Junín (21.37 %). The CYP2D6*3 (rs35742686, 2549A>del) and CYP2D6*4 (rs3892097, 1846G>A) alleles were genotyped by Real Time-PCR with TaqMan® probes; the metabolizing phenotypes were inferred from the genotypes. CYP2D6*3 and CYP2D6*4 were observed with a frequency of 1.5 % (chi-square test X2 0.0539; one degree of freedom) and 5.1% (X2 3.46; one degree of freedom; p-value > 0.05), respectively. By stratification of regions, it was evident that the CYP2D6*4 carriers (X2 20.8263) from Junín are not in Hardy-Weinberg equilibrium (HWE); however, in the global analysis the frequencies for both polymorphisms were in HWE (X2 <3.84). 11.55% of the subjects were classified as intermediate metabolizers (CYP2D6*1/*3 or CYP2D6*1/*4) with an activity score 0<X<1.25, and 0.85% as poor metabolizers (CYP2D6*4/*4). It is concluded that the frequencies of the CYP2D6*3 and CYP2D6*4 polymorphisms are low and expected for the Peruvian mestizo population with tricontinental and Latin American ancestry. Due to the metabolizers described, these findings are relevant in clinical practice.
The cytochrome P450 2D6 (CYP2D6) gene is highly polymorphic that encodes enzymes that metabolize more than 25 % of drugs in clinical use; CYP2D6*3 and CYP2D6*4 being the most relevant polymorphisms in Latin America. The objective of the research was to evaluate the CYP2D6 polymorphism in the Peruvian mestizo population. This study is an observational, descriptive, cross-sectional study with prospective recruitment, non-probabilistic sampling for convenience and consecutive inclusion. The sample was made up of 234 Peruvian mestizo volunteers (men: n= 174; 74.36 %; women: n = 60; 25.64 %) of them, 134 were residents of Lima (57.26 %), 50 from Tacna (21.37 %), and 50 de Junín (21.37 %). The CYP2D6*3 (rs35742686, 2549A>del) and CYP2D6*4 (rs3892097, 1846G>A) alleles were genotyped by Real Time-PCR with TaqMan® probes; the metabolizing phenotypes were inferred from the genotypes. CYP2D6*3 and CYP2D6*4 were observed with a frequency of 1.5 % (chi-square test X2 0.0539; one degree of freedom) and 5.1% (X2 3.46; one degree of freedom; p-value > 0.05), respectively. By stratification of regions, it was evident that the CYP2D6*4 carriers (X2 20.8263) from Junín are not in Hardy-Weinberg equilibrium (HWE); however, in the global analysis the frequencies for both polymorphisms were in HWE (X2 <3.84). 11.55% of the subjects were classified as intermediate metabolizers (CYP2D6*1/*3 or CYP2D6*1/*4) with an activity score 0<X<1.25, and 0.85% as poor metabolizers (CYP2D6*4/*4). It is concluded that the frequencies of the CYP2D6*3 and CYP2D6*4 polymorphisms are low and expected for the Peruvian mestizo population with tricontinental and Latin American ancestry. Due to the metabolizers described, these findings are relevant in clinical practice.
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