A human post-mortem study examined allele-specific mRNA expression from heterozygous individuals with the A118G polymorphism and found significant reductions in mRNA transcribed from the G118 allele. Additionally, the authors transiently expressed both variants of the MOPR in CHO cells and showed a reduction in mRNA and protein expression with the G118 allele (Zhang et al., 2005). The mechanisms underlying the decrease in expression is unclear. As the mutation occurs in a coding region, rather than a promotor, it might seem unlikely that transcription would be affected. However, using in silico tools (bioinformatics), it has been proposed that the A118G SNP may inactivate three transcription factor binding sites while creating two new ones, including a p53 site (Pang et al., 2009), suggesting that cis-acting factors could explain the alterations in expression. While transcriptional regulation using exonic sequence is rare, some examples do exist. Using Mfold technology, in which theoretical mRNA folding can be evaluated for different sequences, it was shown that the G118 variant demonstrated altered folding compared to other permutations which could affect mRNA stability (Johnson et al., 2008; Zhang et al., 2005).
