We do not have any evidence to explain how the −1250G/1032A haplotype contributes to increased requirements for rescue analgesics compared with other haplotypes. One might infer that the G-1250A SNP in the putative regulatory region could be related to some moderate functional alteration, and the −1250G and 1032A alleles could be risk factors for decreased sensitivity to analgesics. Both alleles might combine synergistically to cause profound decreases in sensitivity to analgesics. Future functional studies focusing on both the G-1250A and A1032G SNPs are required to investigate this hypothesis.
