Despite the large amount of evidence supporting a role for A118G in the pharmacogenetics of opioid analgesics, other trials have failed to replicate the findings [35-40]. Two studies even found that women with the A/A genotype needed more fentanyl or sufentanil to achieve analgesia during labor [41, 42]. A meta-analysis of 8 previous studies found no association between the frequency of the G allele and analgesia, but did note a potentially significant effect of the G/G genotype [43]. Taken in aggregate these findings still suggest that A118G genotype may have a recessive effect on the doses of specific opioid medications required for analgesia from particular painful stimuli. Given the different types of painful stimuli and the wide range of available analgesics, however, the extent to which this effect is widely applicable is not clear. Other polymorphisms have also been associated with the efficacy of opioid analgesics. Patients with the G allele at rs9384179 require less fentanyl to achieve analgesia in the 24 hour period following surgery [23]. The analgesic effect of opioid medications after surgery was also associated with the genotypes at rs634479, rs499796, rs548646, and rs679987, which are all located in introns [44].
