The vast majority of pharmacogenetic studies on OPRM1 have analyzed the effects of A118G. As one of the first genetic variants to be associated with pharmacological outcome and a relatively common non-synonymous SNP, the focus on A118G in pharmacogenetic trials is certainly understandable. However, intronic and synonymous coding variants in many genes have been shown to have important effects on transcription, mRNA stability, and splicing, thus affecting gene function despite not directly disrupting any specific residue. OPRM1 has numerous genetic and structural variations, all of which are potential relevant to the field of pharmacogenetics. The small number of studies analyzing OPRM1 polymorphisms other than A118G have revealed some effects on treatment efficacy [23, 44, 70]. By focusing on A118G and overlooking other variation in the gene, a significant portion of OPRM1's role in pharmacogenetics is likely being missed. As high throughput sequencing and other large scale genotyping methods become increasingly common, future studies can and must start to focus on all of the genetic variation present in the ORPM1 gene.
