Unraveling the functional role of the orphan solute carrier, SLC22A24 in the transport of steroid conjugates through metabolomic and genome-wide association studies

• DOI: 10.1371/journal.pgen.1008208
• Publication Date: 2019-09-25T17:34:05Z
• Authors: Sook Wah Yee; Adrian Stecula; Huan-Chieh Chien; Ling Zou; Elena V. Feofanova; Marjolein van Bor...; Kit Wun Kathy Cheung; Noha A. Yousri; Karsten Suhre; Jason M. Kinchen; Eric Boerwinkle; Roshanak Irannejad; Bing Yu; Kathleen M. Giaco...
• Keywords: Genome-wide Association Study; Etiocholanolone; Steroid hormone

Variation in steroid hormone levels has wide implications for health and disease. The genes encoding the proteins involved disposition represent key determinants of interindividual variation ultimately, their effects. Beginning with metabolomic data from genome-wide association studies (GWAS), we observed that genetic variants orphan transporter, SLC22A24 were significantly associated androsterone glucuronide etiocholanolone (sentinel SNPs p-value <1x10-30). In cells over-expressing human or various mammalian orthologs SLC22A24, showed conjugates bile acids substrates transporter. Phylogenetic, genomic, transcriptomic analyses suggested a specialized role kidney appears to function reabsorption organic anions, particular, anionic steroids. Phenome-wide analysis functional are disease such as cardiovascular diseases acne, which have been linked dysregulated metabolism. Collectively, these genomic reveal previously uncharacterized protein homeostasis, opening up new possibilities pharmacological target regulating levels.