The Role of Abcb5 Alleles in Susceptibility to Haloperidol-Induced Toxicity in Mice and Humans
Fig 1
A pharmacogenetic factor for HIT.
(A) The average latency measured after 30 days of haloperidol administration to 17 inbred strains is shown in the top panel. The bottom panel shows ten genes whose genetic pattern was most highly correlated with the latency data by the HBCGM program. The genes within correlated haplotype blocks are indicated by their symbol; an orange, yellow, or white background indicates whether SNPs causing a significant, minor, or no amino acid change are present, respectively. (A blue background indicates a SNP that affects a potential splice site alteration is present.) The haplotypic pattern is shown as colored rectangles that are arranged in the same order as the input data. Strains with the same colored rectangle have the same haplotype within the block. The p-values and genetic effect size were calculated as previously described [14]. (B) Missense SNPs in Abcb5. The 1,255 amino acids in Abcb5 contain two transmembrane (shaded blocks) and two ATP binding transporter domains (solid blocks). The alleles in eight missense SNPs in the 17 analyzed strains are shown, and the alleles that differ from the C57BL/6 reference strain are highlighted. The Gly170Cys is within the first transmembrane domain, and Gly491Ser and Lys493Glu are within the first transporter domain. These three SNPs divide the strains into three haplotypic groupings (each indicated by a different color) that correspond with the haloperidol-induced latency.