Comparative description of haplotype structure and genetic diversity of MDR1
"Comparative description of haplotype structure and genetic diversity of MDR1 (ABCB1) in HIV-positive and HIV-negative populations"
Infect Genet Evol. 2010 Jan
Benish RL, Rodriguez B, Zimmerman PA, Mehlotra RK.
Center for Global Health & Diseases, School of Medicine, Case Western Reserve University, Cleveland
Human P-glycoprotein (P-gp), encoded by MDR1 (ABCB1), is an efflux transporter with a wide specificity for substrates/drugs, including HIV protease inhibitors which are commonly used in HIV/AIDS treatment. Three single nucleotide polymorphisms (SNPs) in MDR1 have been shown to affect P-gp expression and function, and may affect HIV/AIDS treatment outcome: 1236C>T [G412G, exon-12], 2677G>T/A [A893S/T, exon-21] and 3435C>T [I1145I, exon-26]. In the present study, our aims were (i) to compare the 3-SNP MDR1 haplotype structure and genetic diversity between North American HIV-positive and HIV-negative individuals belonging to four major ethnic groups and (ii) to determine whether the haplotype structure and genetic diversity observed in these ethnically admixed populations differ from that in ethnically non-admixed populations. For these aims, we analyzed a cohort of 447 HIV/AIDS patients (White [n=193], Black [n=235], Hispanic [n=17], and Asian [n=2]). Results obtained for these patients were compared with the results for (i) HIV-negative individuals (n=356) and (ii) various HapMap and Environmental Genome Project populations. We observed that the genetic characteristics of MDR1 were largely consistent between HIV-positive and HIV-negative populations, but there were striking interethnic differences in the genetic characteristics of MDR1 in both populations. Although it appeared that the genetic characteristics of MDR1 were largely consistent between ethnically admixed and non-admixed populations, genetic characterization of the admixed populations remains to be done. Thus, our results provide useful comparative insights about the genetic characteristics of MDR1 that could be extrapolated across population groups worldwide. For a meaningful interpretation of these results regarding HIV/AIDS treatment outcome, MDR1 haplotype/diplotype structure data, genetic characterization of population admixture, and polymorphisms in other relevant drug transporter and/or metabolizing enzyme genes should be considered in future clinical studies.
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