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Chunk #17 — Results — Investigation of ADME eQTLs

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Genomics of ADME gene expression: mapping expression quantitative trait loci relevant for absorption, distribution, metabolism and excretion of drugs in human liver.
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Table 2 shows the 74 ADME associations (68 cis-acting and 6 trans-acting) uniquely identified in our study, which mapped to 31 different trait genes. Closer analysis showed that the corresponding SNPs had indeed been analyzed but were not significantly associated with expression in the former study.16 These unique associations included additional SNPs for traits mentioned in Table 1 but with LD of r2<0.8 (for example, ARNT, several GSTs, VKORC1) and additional ADME and ADME-related genes including the histamine and diamine-oxidizing copper enzyme ABP1, the arachidonic acid-metabolizing CYP4F12, the flavin monooxygenase FMO4, thymodylate synthase (ENOSF1/TYMS) involved in 5-fluorouracil response and the solute carrier SLC22A10, among others. Furthermore, UGT1A1 expression was associated with rs2070959 (located in UGT1A6), which is closely linked (r2=0.87) to rs8175347, the causal SNP of the UGT1A1*28 allele.44 Remarkably, this well-known polymorphism had not been detected by the Seattle study.16 Box plots of these unique eQTLs represented by one SNP each are shown in Supplementary Figure S1.