Polimorfismos del gen de resistencia a múltiples drogas (MDR1) en poblaciones chilenas: mapuche, mestiza y maorí
Background: There are significant differences in drug responses among different ethnic groups. The multidrug transporter P-gp, encoded by the MDR1 gene, plays a key role in determining drug bioavailability, and an association between a polymorphism in exon 26 (C3435T) and lower P-gp expression has b...
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| Autores principales: | , , |
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| Lenguaje: | Spanish / Castilian |
| Publicado: |
Sociedad Médica de Santiago
2004
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| Materias: | |
| Acceso en línea: | http://www.scielo.cl/scielo.php?script=sci_arttext&pid=S0034-98872004000900006 |
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| Sumario: | Background: There are significant differences in drug responses among different ethnic groups. The multidrug transporter P-gp, encoded by the MDR1 gene, plays a key role in determining drug bioavailability, and an association between a polymorphism in exon 26 (C3435T) and lower P-gp expression has been found. The co-segregation of this polymorphism with the polymorphism in exon 12 (C1236T) and in exon 21 (G2677T/A) determines several MDR1 haplotypes in humans. Aim: To characterize the polymorphisms of exons 26, 21 and 12 of the MDR1 gene in different Chilean populations. Material and methods: Using a polymerase chain reaction and restriction fragment length polymorphism technique, we studied the allelic frequencies and the distribution of MDR1 haplotypes in 3 Chilean populations: Mestizo (n=104), Mapuche (n=96, living in the National Reservation of the Huapi Island, Ranco Lake) and Maori (n=52, living in Eastern Island). Results: The frequency of the normal MDR1*1 haplotype, without mutations, was lower in Mapuches than in Mestizos or Maoris (p <0.005) but similar to that reported in Asian population (p=0.739), probably due to the Asian origin of the Amerindian populations. In addition, the MDR1*l haplotype frequency in Mestizos was similar to the frequency reported in Caucasians (p=0.49), in agreement with the origin of our population, with a strong influence of Caucasian genes from the Spanish conquerors. The MDR1*2 haplotype distribution, with the three polymorphisms and probably lower multidrug transporter expression, was similar in the three Chilean populations studied (p >0.05), but lower than the frequencies reported in Caucasians or Asians (p <0.05). Conclusions: We found significant differences in the frequencies of genetic polymorphisms of the MDR1 gene in Chilean populations, related to the ethnic origins of our ancestors (Rev Méd Chile 2004; 132: 1061-8 |
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