Another potential source of functional diversity is splice variants. At least half of the genome is expressed in alternatively spliced isoforms14 and gene functions may also be modified by SNPs in alternatively spliced exons. A number of OPRM1 alternatively spliced variants have been reported in rodents and humans.15-20 The receptors encoded by two human splice variants that retain different parts of intron 1 were shown to form heterodimers with the wild type protein.19 An alternatively spliced exon with an alternative promoter, in the 5′ upstream region (~28-30 kb), was identified in rodents and humans, along with cell-specific splice variants.15, 19, 21-23 A SNP in intron 1 showed an effect on the OPRM1 gene expression in vitro and was associated with pain sensitivity.20
