Chatti Imen, Woillard Jean-Baptiste, Mili Amira, Creveaux Isabelle, Ben Charfeddine Ilhem, Feki Jihène, Langlais Sarah, Ben Fatma Leila, Saad Ali, Gribaa Moez, Libert Frédéric
Laboratory of Human Cytogenetics, Molecular Genetics and Reproductive Biology, Farhat Hached Hospital, Sousse, Tunisia.
U850 INSERM, University of Limoges, CHU Limoges, FHU SUPORT, Limoges, France.
Iran J Public Health. 2017 Dec;46(12):1704-1711.
Pain and its opioid treatments are complex measurable traits. Responses to morphine in terms of pain control is likely to be determined by many factors, including the underlying pain sensitivity of the patient, along with nature and extent of the painful process, concomitant medications, genetic and other clinical and environmental factors. This study investigated genetic polymorphisms implicated in the inter-individual pain response variability to opioid treatment in the Tunisian population.
This prospective association study investigated seven variations in the , and gene, which encode Mu and KAPPA opioid receptors, and Catechol-O-methyltransferase enzyme respectively, in a cohort of 129 Tunisian cancer pain patients under oral morphine treatment. Genotyping was performed by simple probe probes on Light Cyler for rs17174629, rs1799972, rs1799971, rs1051659, rs1051660 and rs4680 and by PCR assay for the indel in the promoter region of OPRK1 (rs35566036). A statistical associations study between dose (continuous), dose escalation (yes/no) and SNP or haplotypes were investigated using linear multiple regressions and logistic regressions respectively adjusted on metastases and pain covariates in the R software.
We detected significant association of the rs1051660 adjusted on metastasis and pain (=0.02), no other association has been detected between the 7 polymorphisms screened and the dose of morphine needed for pain relief.
This can be explained by the strong genetic heterogeneity in the cosmopolitan areas where our patients were recruited for this study, compared to more homegenous population recruited in other studies.
疼痛及其阿片类药物治疗是复杂的可测量特征。在疼痛控制方面对吗啡的反应可能由许多因素决定，包括患者潜在的疼痛敏感性、疼痛过程的性质和程度、伴随用药、遗传以及其他临床和环境因素。本研究调查了突尼斯人群中与阿片类药物治疗个体间疼痛反应变异性相关的基因多态性。
这项前瞻性关联研究在129名接受口服吗啡治疗的突尼斯癌症疼痛患者队列中，调查了分别编码μ和κ阿片受体以及儿茶酚 - O - 甲基转移酶的基因中的7个变异。通过在Light Cyler上使用简单探针进行基因分型检测rs17174629、rs1799972、rs1799971、rs1051659、rs1051660和rs4680，通过PCR检测OPRK1启动子区域的插入缺失（rs35566036）。分别使用线性多元回归和逻辑回归在R软件中对转移和疼痛协变量进行调整，研究剂量（连续变量）、剂量递增（是/否）与单核苷酸多态性（SNP）或单倍型之间的统计关联。
我们检测到经转移和疼痛调整后的rs1051660存在显著关联（P = 0.02），在筛选的7个多态性与缓解疼痛所需吗啡剂量之间未检测到其他关联。
这可以解释为与其他研究中招募的基因更同质的人群相比，本研究招募患者的世界性地区存在很强的遗传异质性。
