Haplotype analysis revealed that SNPs rs510769 and rs3778151 are part of a haplotype block that spans intron 1. Several SNPs at the -20 kb 5′ region (including SNP rs1074287) are in high LD with this haplotype block (Levran et al. 2011). Several lines of evidence suggest a special functionality to intron 1 (Choi et al. 2006; Shabalina et al. 2009). A potential functional SNP in intron 1 (rs563649) is shown to be located within a structurally conserved internal ribosome entry site (IRES) in the 5′ UTR of a novel exon 13 in an OPRM1 isoform and to affect both mRNA levels and translation efficiency. This SNP was also associated with pain perception (Shabalina et al. 2009). A (CA) repeat in intron 1 was associated with substance dependence (alcohol, cocaine or opioid) in EAs, but not in AAs (Kranzler et al. 1998).
