Genetic characterization of nucleoside analogue transporters ABCC4 and ABCC5 gene loci

Abstract

Linkage disequilibrium (LD) between unknown functional variants and genotyped markers enables association studies to assess correlation between variants and phenotypes of human traits. To facilitate future association studies, a multiplex minisequencing genotyping method was established for the characterization of LD and haplotype architecture of multiple polymorphisms around ABCC4 and ABCC5 in five populations of different ethnicities. These two genes encode for ATP-binding membrane transporters demonstrated to efflux cyclic nucleotides and nucleotide analogues useful for antiviral therapy and chemotherapy. A modest number of population-specific tagging SNPs was defined which could be directly applied to studies associating disease/drug response and these genes. The final strategy to detect evidence of recent positive selection singularized the allele A of SNP i-1 -1015G>A within the putative promoter region of ABCC4 in an European-American population. The use of these strategies in haplotype association studies would augment efforts in disclosing the functional variants within these genes.