Gong Xiao-Di, Wang Jiong-Yi, Liu Feng, Yuan Hai-Hua, Zhang Wen-Ying, Guo Yue-Hui, Jiang Bin
Department of Oncology, Shanghai Third People's Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
Asian Pac J Cancer Prev. 2013;14(5):2937-43. doi: 10.7314/apjcp.2013.14.5.2937.
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.
OPRM1基因A118G多态性和ABCB1基因C3435T多态性被认为与慢性疼痛患者的疼痛敏感性、阿片类药物使用、耐受性和依赖性以及不良反应发生率的个体差异有关。本研究旨在探讨这两种多态性与中国癌症疼痛患者阿片类药物需求量之间的关联。
分别采用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)和直接测序法,对112例癌症相关疼痛患者的rs1799971(OPRM1)和rs1045642(ABCB1)基因型进行检测。根据情况,采用t检验或单因素方差分析对不同基因型或等位基因组进行比较。采用趋势Jonckheere-Terpstra检验分析等位基因数量与阿片类药物反应之间的潜在关系。
在112名受试者中,118G变异等位基因和3435T等位基因的频率分别为38.4%和37.9%。GG基因型(P=0.0004)和AG+GG基因型(P=0.005)患者的24小时阿片类药物剂量显著高于AA携带者。显性突变118G等位基因倾向于与24小时阿片类药物剂量逐渐增加相关(P=0.001)。与CC/CT基因型患者相比,ABCB1基因TT基因型患者接受的24小时和体重-体表面积校正的24小时阿片类药物剂量更高(分别为P=0.057和0.028)。
OPRM1基因A118G单核苷酸多态性(SNP)是中国癌症疼痛患者阿片类药物需求量个体差异的关键因素。这可能也适用于ABCB1基因C3435T SNP。