The human multidrug resistance gene (MDR1) encodes for P-glycoprotein (P-gp) which is a transmembrane transporter protein that acts as an efflux pump for a number of lypophilic compounds. It plays a protective role for cells against DNA damage. The wobble C3435T polymorphism at exon 26 has been associated with different expression levels and activity. Differences in allele frequency of the C3435T polymorphism have been demonstrated between distinct ethnic groups. In our study we examined these polymorphisms in 433 healthy individuals. From these, 229 were Central American mestizos from Nicaragua (n = 117) and El Salvador (n = 112) to be compared with a group of 204 North Spaniards, with the aim of detecting potential genotypic differences between these populations. The genotypes were determined by PCR-RFLP. The frequencies of the C allele were very similar among Central Americans (0.53) and Spaniards (0.52), which is consistent with the ethnic origin of Central American individuals (Amerindians and European Caucasians). In comparison to other previously studied populations, the C allele frequency in Central Americans was significantly lower than that found in African populations and higher than that observed in the Indian and Southwest Asian populations. These data may be relevant for dose recommendation of P-gp substrate drugs and also for studies of allele disease association in the Central American population.

译文

人类多药耐药基因 (MDR1) 编码P-糖蛋白 (P-gp),P-糖蛋白是一种跨膜转运蛋白,可作为许多嗜酸性化合物的外排泵。它对细胞免受DNA损伤起保护作用。外显子26的摆动C3435T多态性与不同的表达水平和活性有关。已在不同种族之间证明了C3435T多态性的等位基因频率差异。在我们的研究中,我们在433健康个体中检查了这些多态性。从这些229中,将尼加拉瓜 (n = 117) 和萨尔瓦多 (n = 112) 的中美洲混血儿与一组204的北西班牙人进行比较,目的是检测这些人群之间的潜在基因型差异。通过pcr-rflp确定基因型。C等位基因的频率在中美洲 (0.53) 和西班牙人 (0.52) 之间非常相似,这与中美洲个体 (美洲印第安人和欧洲高加索人) 的种族起源一致。与其他先前研究的人群相比,中美洲人的C等位基因频率明显低于非洲人群,高于印度和西南亚人群。这些数据可能与P-gp底物药物的剂量推荐有关,也与中美洲人群的等位基因疾病关联研究有关。

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