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Genetic variables could include serotonergic genes (serotonergic receptors [5HT2a]; serotonin transporter 5HTlPR); endorphinergic genes (mu OPRM1 gene; proenkephalin [PENK, PENK polymorphic 3' UTR dinucleotide (CA) repeats]; GABergic gene (GABRB3), and dopaminergic genes (ANKKI Taq A; DRD2 C957T, DRD4 7R, COMT Val/met substation; MAO-A uVNTR; and SLC6A3 9 or 10R).
CpG methylation inhibits proenkephalin gene expression and binding of the transcription factor AP-2.
Met- and Leu-enkephalin are produced from the precursors proenkephalin A and B and prodynorphin; neurons that synthesize proenkephalin are widely distributed in brain.