The A/A genotype in the A1032G SNP was significantly associated with increased postoperative analgesic requirements in our study. The G allele appears to be dominant in mediating the transmission of intensified opioid signaling compared with the A allele. However, this particular SNP is synonymous and causes no amino acid change; therefore, the protein structure encoded by this gene may not be altered by this SNP. Nevertheless, local structural difference in the 1023–1059 position was observed between the sequences, including 1032A and 1032G, in our prediction of the KCNJ6 mRNA secondary structure (Figure S1). Whereas the 1032A mRNA formed an interior loop, a hairpin loop, and a 6 bp helix, the 1032G mRNA formed a bulge loop as well as an interior loop, a hairpin loop, and a 7 bp helix in the local structure. Although the role of this difference in gene function remains to be determined, the SNP may actually influence mRNA expression level. Indeed, recent studies measuring allelic expression imbalances [35] have demonstrated that even a synonymous SNP could affect mRNA and protein levels [36], possibly by altering mRNA stability and protein synthesis [37]. Similar mRNA and protein levels, but altered conformations, were found for synonymous polymorphisms [38].
