OBJECTIVES AND STUDY DESIGN: The genetic basis of two polymorphisms of drug- and carcinogen-metabolizing enzymes, NAT2 (arylamine N-acetyltransferase-2) and CYP2E1 (cytochrome P450 2E1), was studied in genomic deoxyribonucleic acid from 137 healthy, unrelated subjects from a mixed Nicaraguan population. RESULTS: Six point mutations were identified at the coding region of the NAT2 gene, including the most common alleles NAT2*4 (41.6%), NAT2*5B (31.4%), and NAT2*6A (16.8%). The percentage of carriers of two defective genes was 49.6%. The Nicaraguan population studied was in Hardy-Weinberg's disequilibrium for the NAT2 genotype (p < 0.01) and the allele frequencies were significantly different from those of other populations, being intermediate between those of pure Central American Indians and Spanish persons. The frequency of CYP2E1 alleles mutated at the RsaI site (c2 allele; 16.5%) was intermediate between that of Spanish white and Asian subjects. About 5% of the subjects were homozygous for the c2 allele. CONCLUSIONS: These findings indicate a high impact of genetic admixture of populations of Asian origin (Central American Indians) and white persons (Spaniards) on the genetic polymorphisms studied here and suggest that among mixed Hispanics a high heterogeneity of genotypes and phenotypes can be expected depending on the degree of genetic admixture of every subgroup. Therefore different subgroups of mixed Hispanic subjects can exhibit different results when treated with drugs that are inactivated through polymorphic enzymes.
OBJECTIVES AND STUDY DESIGN: The genetic basis of two polymorphisms of drug- and carcinogen-metabolizing enzymes, NAT2 (arylamine N-acetyltransferase-2) and CYP2E1 (cytochrome P450 2E1), was studied in genomic deoxyribonucleic acid from 137 healthy, unrelated subjects from a mixed Nicaraguan population. RESULTS: Six point mutations were identified at the coding region of the NAT2 gene, including the most common alleles NAT2*4 (41.6%), NAT2*5B (31.4%), and NAT2*6A (16.8%). The percentage of carriers of two defective genes was 49.6%. The Nicaraguan population studied was in Hardy-Weinberg's disequilibrium for the NAT2 genotype (p < 0.01) and the allele frequencies were significantly different from those of other populations, being intermediate between those of pure Central American Indians and Spanish persons. The frequency of CYP2E1 alleles mutated at the RsaI site (c2 allele; 16.5%) was intermediate between that of Spanish white and Asian subjects. About 5% of the subjects were homozygous for the c2 allele. CONCLUSIONS: These findings indicate a high impact of genetic admixture of populations of Asian origin (Central American Indians) and white persons (Spaniards) on the genetic polymorphisms studied here and suggest that among mixed Hispanics a high heterogeneity of genotypes and phenotypes can be expected depending on the degree of genetic admixture of every subgroup. Therefore different subgroups of mixed Hispanic subjects can exhibit different results when treated with drugs that are inactivated through polymorphic enzymes.
Authors: Carolina Céspedes-Garro; María-Eugenia G Naranjo; Fernanda Rodrigues-Soares; Adrián LLerena; Jorge Duconge; Lazara K Montané-Jaime; Hilda Roblejo; Humberto Fariñas; María de Los A Campos; Ronald Ramírez; Víctor Serrano; Carmen I Villagrán; Eva M Peñas-LLedó Journal: Pharmacogenomics Date: 2016-09-16 Impact factor: 2.533
Authors: R Salazar-González; R Gómez; S Romano-Moreno; S Medellín-Garibay; A Núñez-Ruíz; M Magaña-Aquino; R C Milán-Segovia; D P Portales-Pérez Journal: Mol Biol Rep Date: 2014-08-28 Impact factor: 2.316
Authors: Mary M Jenkins; Jennita Reefhuis; Margaret L Gallagher; Jennifer G Mulle; Thomas J Hoffmann; Deborah A Koontz; Cynthia Sturchio; Sonja A Rasmussen; John S Witte; Patricia Richter; Margaret A Honein Journal: Am J Med Genet A Date: 2014-03-25 Impact factor: 2.802