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Chunk #33 — Discussion

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Association between KCNJ6 (GIRK2) gene polymorphisms and postoperative analgesic requirements after major abdominal surgery.
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KCNJ6 A1032G on the frequency of rescue analgesic administration was 0.012 after the Bonferroni correction. This suggests that this SNP is likely to affect sensitivity to analgesics, although we must concede that this significance might possibly occur by chance alone. Patients who experienced more severe pain, evaluated by NRS pain scores, required higher-dose and more frequent rescue analgesics, although significant associations were not observed between the A1032G SNP or −1250G/1032A haplotype and NRS pain scores. Moreover, KCNJ6 gene expression levels in the 1032A/A subjects was significantly decreased compared with 1032A/G and 1032G/G subjects in the real-time qPCR analysis using human brain tissues, suggesting that the 1032A/A subjects required more analgesics because of lower KCNJ6 gene expression levels and consequently insufficient analgesic effects. Altogether, these results suggest that subjects carrying the A/A genotype in the A1032G SNP or −1250G/1032A haplotype, especially in females, had lower sensitivity to analgesics and, therefore, required more rescue analgesics than subjects carrying other genotypes or haplotypes to achieve a similar degree of pain relief.