Increased transcription was demonstrated for transcripts related to lipid and cholesterol metabolism, except for two transcripts encoding proteins that reduce available cholesterol in the cell by excretion or metabolism. Expression of transcripts encoding the first specific step in the cholesterol biosynthetic pathway (FDFT1), the high-density lipoprotein (HDL) receptor (SCARB1) and an inhibitor of cholesterol biosynthesis (PRKAB1) were increased. Of particular note were increases in the apoliprotein L (APOL) transcripts, for which the increased expression of APOL2 was validated by QPCR ( Fig. 3 ). APOL family proteins are HDLs, which play a central role in cholesterol transport and homeostasis. The six known APOL genes are exclusively present in primates, with the APOL1-4 genes forming a tight cluster on human chromosome 22q13.1 [30]. The APOL2 transcript is most highly expressed in brain, while the APOL1 transcript differs from other APOL transcripts by an additional exon that produces a secreted APOL protein [30]. These differences may also underlie the opposite changes in the APOL1 and APOL2 transcripts in the drug abuse cases. APOL4 was significantly increased only in the cocaine cases.
