The best candidate SNP, rs2952768, is located closer to the METTL21A (FAM119A) gene than to the CREB1 gene on chromosome 2 (Figures 1a and b). However, no significant association was found between rs2952768 and METTL21A mRNA expression, precluding the attribution of phenotypic alterations related to this SNP to the expression levels of the METTL21A gene. Although the precise functions of METTL21A are poorly understood to date, a representative METTL, METTL11A, reportedly exhibited catalytic activity as a histone methyltransferase42 and chronic morphine treatment exhibited the acetylation and trimethylation of histones.43 Although future studies are imperative, the action of opioids might be partially modulated by histone methylation via METTL functions.
