Gene Polymorphisms of OPRM1 A118G and ABCB1 C3435T May Influence Opioid Requirements in Chinese Patients with Cancer Pain

Xiao-Di Gong,Jiong-Yi Wang,Yue-Hui Guo,Bin Jiang,Hai-Hua Yuan,Feng Liu,Wen-Ying Zhang

doi:10.7314/apjcp.2013.14.5.2937

Xiao-Di Gong, Jiong-Yi Wang + Show 5 more

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https://doi.org/10.7314/apjcp.2013.14.5.2937

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Abstract

Polymorphisms of OPRM1 A118G and ABCB1 C3435T have been suggested to contribute to inter-individual variability regarding pain sensitivity, opioid usage, tolerance and dependence and incidence of adverse effects in patients with chronic pain. This study aimed to investigate the association of both two polymorphisms with opioid requirements in Chinese patients with cancer pain. The genotypes of rs1799971 (OPRM1) and rs1045642 (ABCB1) were determined by PCR-RFLP and direct sequencing methods respectively in 112 patients with cancer-related pain. Comparisons between the different genotype or allele groups were performed with t-tests or one-way ANOVA tests, as appropriate. The potential relationship of allele number with opioid response was performed with a trend Jonckheere-Terpstra test. In the 112 subjects, the frequencies of variant 118 G and 3435T allele were 38.4% and 37.9%, respectively. Significant higher 24h-opioid doses were observed in patients with GG (P=0.0004) and AG + GG (P=0.005) genotypes than the AA carriers. The dominant mutant 118G allele tended to be associated with progressively increasing 24h-opioiddoses (P=0.001). Compared with CC/CT, patients with ABCB1 TT genotype received higher 24h- and weight-surface area-adjusted-24h- opioids doses (P=0.057 and 0.028, respectively). The OPRM1 A118G single nucleotide polymorphism (SNP) is a key contributor for the inter-individual variability in opioidrequirements in Chinese cancer pain patients. This may possibly extend to the ABCB1 C3435T SNP.

Highlights

According to statistics by WHO, about 60%~90% of patients with advanced cancer are suffered from cancer pain in varying degrees, which is a presenting symptom in 70% patients (Elliott et al, 1999)
This study aimed to investigate the association of both two polymorphisms with opioid requirements in Chinese patients with cancer pain
The pain duration of TT carriers was much longer than that of those with C allele (Sia et al, 2010). Functional consequences of both single nucleotide polymorphism (SNP) haven’t yet come to a consensus. Based on these above researches, in this study we focused on the differences in consumptions and analgesia effects of opioids across various SNPs of OPRM1 or ATP-binding cassette B1 gene (ABCB1) gene

Summary

Introduction

According to statistics by WHO, about 60%~90% of patients with advanced cancer are suffered from cancer pain in varying degrees, which is a presenting symptom in 70% patients (Elliott et al, 1999). Recent studies suggests that polymorphisms of mu opioid receptor gene (OPRM1) and ATP-binding cassette B1 gene (ABCB1) (multidrug resistance 1 [MDR1]) have a significant association with the analgesia effects and consumptions of opioids (Uhl et al, 1999; Campa et al, 2008; Lloret et al, 2011; Kasai et al, 2011; Haerian et al, 2013). Plenty of studies have indentified that the haplotype of OPRM1 includes more than 100 polymorphisms, in which only A6V, A118G (N40D), R260H, R265H, S268P are involved in analgesia effect (Hoehe et al, 2000; Befort et al, 2001; Wang et al, 2001). A118G nonsynonymous polymorphism has been undergoing most thorough study which makes MOPR lose a glycosylation site but enhance its affinity to opioids. The 118G tended to be correlated with the reduced analgesic effects, efficiency and much less side effects induced by morphine and its active metabolite -M6G (Lötsch et al, 2006; Campa et al, 2008)

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