Many studies provided evidence for the importance of the OPRM1 118A>G polymorphism in addiction, pain, HPA activation, and treatment response.e.g., 2-9 These studies have shown mixed results regarding the association between the 118G variant and opioid dependence, opioid analgesia and opioid adverse effects.40 Most studies have used single SNP analyses and were generally limited to the coding region or to the proximal upstream region. Several studies employed haplotype analysis but were also limited to specific regions. Hoehe et al. performed a comprehensive haplotype analysis of OPRM1 but the study did not include SNPs from intron 1 and was limited to the proximal 5′ region (−2.4 kb). 26 Lue et al. studied five variants from the proximal 5′ flanking region (−2 kb) and two SNPs from exon 1. 27 Zhang et al. examined 13 SNPs spanning the coding sequence including several SNPs from intron 1, but none in the 5′ flanking region. 29, 30 Xuei et al. genotyped 18 SNPs including one in the proximal 5′ region (−6 kb). 41 A recent study used a haplotype-based approach to predict response to
