Influence of genetic admixture on polymorphisms of drug-metabolizing enzymes: analyses of mutations on NAT2 and C gamma P2E1 genes in a mixed Hispanic population.
OBJECTIVE
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.
Martínez
C
C
Department of Pharmacology, Medical School, University of Extremadura, Badajoz, Spain.
Agúndez
J A
JA
Olivera
M
M
Llerena
A
A
Ramirez
R
R
Hernández
M
M
Benítez
J
J
D001191:Arylamine N-Acetyltransferase / Q000235:genetics*; D019392:Cytochrome P-450 CYP2E1 / Q000235:genetics*; D005838:Genotype; D006630:Hispanic or Latino / Q000235:genetics*; D006801:Humans; D009154:Mutation; D009527:Nicaragua; D010641:Phenotype; D011110:Polymorphism, Genetic / Q000235:genetics*
D019392:Cytochrome P-450 CYP2E1; D001191:Arylamine N-Acetyltransferase; C478900:NAT2 protein, human