OPRM1基因A118G多态性对癌痛患者阿片类药物使用剂量影响的Meta分析
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摘要
目的:系统评价μ阿片受体基因(OPRM1)A118G多态性对癌痛患者阿片类药物使用剂量的影响,为其个体化用药提供参考。方法:计算机检索The Cochrane Library、PubMed、Embase、Medline、CNKI、WanFang Data和VIP数据库,搜索有关癌痛患者OPRM1基因A118G多态性和阿片类药物使用剂量的相关文献,检索年限均从各数据库建库起至2017年12月31日。由两位评价员独立筛选文献、提取资料、评价纳入研究的偏倚风险后,采用RevMan 5.3软件进行Meta分析。结果:纳入5项研究,共459例患者。OPRM1基因A118G多态性检测结果分为突变纯合子(GG)基因型、野生杂合子(AG)基因型、野生纯合子(AA)基因型。Meta分析结果显示:GG基因型患者阿片类镇痛药的需要量较AG基因型高[SMD=-39.74,95%CI(-59.20,-20.28),P<0.001];GG基因型患者阿片类镇痛药的需要量较AA基因型高[SMD=-48.77,95%CI(-68.01,-29.53),P<0.000 1]。结论:基于目前研究表明OPRM1基因A118G单核苷酸多态性与患者阿片类镇痛药物使用剂量有相关性,携带G等位基因的癌痛患者阿片类药物的使用剂量更多。
Objective: To provide reference for the individualized treatment of opioid drugs by investigating the effects of OPRM1 gene A118G polymorphism on opioids dosage in patients with cancer pain. Methods: The Cochrane Library,PubMed,Embase,Medline,CNKI,WanFang Data and VIP database were searched to collect studies about A118G polymorphism of OPRM1 gene and dose of opioids in patients with cancer pain,the retrieval time was from the establishment to December 31,2017. Two reviewers independently screened literature,extracted data and assessed the risk of bias of included studies. Then,Meta-analysis was performed by RevMan 5. 3 software. Results: A total of five articles with 459 patients were included. Genetic testing showed that OPRM1 gene A118G polymorphism divided into mutant homozygote GG,wild-type heterozygous AG and wild homozygous AA. The results of single group rate meta-analysis showed,the does of opioid analgesics for patients with mutant homozygote GG was higher than the wild-type heterozygous AG [SMD =-39. 74,95% CI(-59. 20,-20. 28),P < 0. 001],the does of opioid analgesics for patients with mutant homozygote GG was higher than wild homozygous AA [SMD =-48. 77,95% CI(-68. 01,-29. 53),P < 0. 000 1]. Conclusion:Based on current research showed that OPRM1 gene A118G single nucleotide polymorphisms were associated with patients carrying the G-allele increased the requirement of opioids.
Objective: To provide reference for the individualized treatment of opioid drugs by investigating the effects of OPRM1 gene A118G polymorphism on opioids dosage in patients with cancer pain. Methods: The Cochrane Library,PubMed,Embase,Medline,CNKI,WanFang Data and VIP database were searched to collect studies about A118G polymorphism of OPRM1 gene and dose of opioids in patients with cancer pain,the retrieval time was from the establishment to December 31,2017. Two reviewers independently screened literature,extracted data and assessed the risk of bias of included studies. Then,Meta-analysis was performed by RevMan 5. 3 software. Results: A total of five articles with 459 patients were included. Genetic testing showed that OPRM1 gene A118G polymorphism divided into mutant homozygote GG,wild-type heterozygous AG and wild homozygous AA. The results of single group rate meta-analysis showed,the does of opioid analgesics for patients with mutant homozygote GG was higher than the wild-type heterozygous AG [SMD =-39. 74,95% CI(-59. 20,-20. 28),P < 0. 001],the does of opioid analgesics for patients with mutant homozygote GG was higher than wild homozygous AA [SMD =-48. 77,95% CI(-68. 01,-29. 53),P < 0. 000 1]. Conclusion:Based on current research showed that OPRM1 gene A118G single nucleotide polymorphisms were associated with patients carrying the G-allele increased the requirement of opioids.
引文
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2 胡晶,沈金芳,吴斌.阿片类药治疗癌痛的疗效与基因多态性的相关性研究进展[J].中国药房,2012,23(18):1706-1707
3 李颖,李翔,罗欢,等.基因多态性对阿片类药物疼痛治疗影响的研究进展[J].中国医院药学杂志,2018,38(2):203-207
4 Ren ZY,Xu XQ,Bao YP,et al.The impact of genetic variation on sensitivity to opioid analgesics in patients with postoperative pain:a systematic review and meta-analysis[J].Pain Physician,2015,18(2):131-152
5 Hajj A,Peoc'h K,Laplanche JL,et al.Genotyping test with clinical factors:better management of acute postoperative pain?[J].Int J Mol Sci,2015,16(3):6298-6311
6 朱敏,潘志强,张璐,等.ABCB1基因多态性与癌痛感知及癌痛病人阿片需求量的关联性分析[J].中国疼痛医学杂志,2017,23(6):426-428
7 Cajanus K,Kaunisto MA,Tallgren M,et al.How much oxycodone is needed for adequate analgesia after breast cancer surgery:effect of the OPRM1 118A>G polymorphism[J].J Pain,2014,15(12):1248-1256
8 Song F,Xiong T,Parekh-Bhurke S,et al.Inconsistency between direct and indirect comparisons of competing interventions:meta-epidemiological study[J].BMJ,2011,343 :d4909
9 Stang A.Critical evaluation of the Newcastle-Ottawa scale for the assessment of the quality of nonrandomized studies in meta-analyses[J].Eur J Epidemiol,2010,25(9):603-605
10 原卫生部.癌症疼痛诊疗规范(2011年版)[J].临床肿瘤学杂志,2012,17(2):153-159
11 Klepstad P,Rakvag TT,Kaasa S,et al.The 118 A>G polymorphism in the humanμ-opioid receptor gene may increase morphine requirements in patients with pain caused by malignant disease[J].Acta Anaesthesiol Scand,2004,48(10):1232-1239
12 Gong XD,Wang JY,Liu F,et al.Gene polymorphisms of OPRM1 A118G and ABCB1 C3435T may inuence opioid requirements in Chinese patients with cancer pain[J].Asian Pac J Cancer Prev,2013,14(5):2937-2941
13 张群,王守星,黄桂春,等.OPRM1基因多态性对癌痛患者使用芬太尼透皮贴剂镇痛效应的影响[J].癌症进展,2015,13(6):615-617
14 李颖,吴飞雪,孙立,等.OPRM1 A118G多态性对我国汉族癌痛患者阿片类药物使用剂量的影响[J].中国药房,2016,27(20):2737-2738
15 李擎,刘勇,于洋,等.μ阿片受体A118G基因多态性预测盐酸羟考酮的镇痛效果[J].医药导报,2016,35(5):481-483
16 Zhang W,Yuan JJ,Kan QC,et al.Study of the OPRM1A118G genetic polymorphism associated with postoperative nausea and vomiting induced by fentanyl intravenous analgesia[J].Minerva Anesthesiol,2011,77(1):33-39
17 Zwisler ST,Enggaard TP,Noehr-jensen L,et al.The antinociceptive effect and adverse drug reactions of oxycodone in humanexperimental pain in relation to genetic variations in the OPRMIand ABCB1 genes[J].Fundam Clin Pharmacol,2010,24(4)517-524
18 Lee SH,Kim JD,Park SA,et al.Effects ofμ-Opioid receptor gene polymorphism on postoperative nausea and vomiting in patients undergoing general anesthesia with remifentanil:Double blinded randomized trial[J].J Korean Med Sci,2015,30(5):651-657
19 Hwang IC,Park JY,Myung SK,et al.OPRM1 A118G gene vatiant and postoperative opioid requirement:a systematic review and meta-analysis[J].Anesthesiology,2014,121(4):825-832
20 Chen D,Liu L,Xiao Y,et al.Ethnic-specific meta-analyses of association between the OPRM1 A118G polymorphism and alcohol dependence among Asinans and Causaians[J].Drug Alcohol Depend,2012,123(1-3):1-6
21 张双全,李少英,谭秀华.μ受体基因118A→G突变对芬太尼椎管内镇痛作用的影响[J].南方医科大学学报,2013,33(2):309-311
22 Matic M,Jongen JL,Elens L,et al.Advanced cancer pain:the search for genetic factors correlated with interindividual variability in opioid requirement[J].Pharmacogenomics,2017,18(12):1133-1142
23 Chatti I,Woillard JB,Mili A,et al.Genetic Analysis of Mu and Kappa Opioid Receptor and COMT Enzyme in Cancer Pain Tunisian Patients Under Opioid Treatment[J].Iran J Public Health,2017,46(12):1704-1711
24 Reyes-Gibby CC,Shete S,Rakvg T,et al.Exploring joint effects of genes and the clinical efficacy of morphine for cancer pain:OPRM1 and COMT gene[J].Pain,2007,130(1-2):25-30
25 Cajanus K,Kaunisto MA,Tallgren M,et al.How much oxycodone is needed for adequate analgesia after breast cancer surgery:effect of the OPRM1 118A>G polymorphism[J].J Pain,2014,15(12):1248-1256
26 Baber M,Chaudhry S,Kelly L,et al.The pharmacogenetics of codeine pain relief in the postpartum period[J].Pharmacogenomics J,2015,15(5):430-435
27 Khalil H,Sereika SM,Dai F,et al.OPRM1 and COMT gene-gene interaction is associated with postoperative pain and opioid consumption after orthopedic trauma[J].Biol Res Nurs,2017,19(2):170-179
28 Hajj A,Halepian L,Osta NE,et al.OPRM1 c 118A>G polymorphism and duration of morphine treatment associated with morerphine doses and quality-of-life in palliative cancer pain settings[J].Int J Mol Sci,2017,18(4):1-17
29 Gong XD,Wang JY,Liu F,et al.Gene polymorphis of OPRM1 A118G and ABCB1 C3435T may influence opioid requirements in Chinese patients with cancer pain[J].Asian Pac J Cancer Prev,2013,14(5):2937-2943
30 罗希,李杏莉,胡佩武,等.μ阿片受体基因多态性与美沙酮维持治疗剂量的关联分析[J].实用预防医学,2016,23(5):513-515
2 胡晶,沈金芳,吴斌.阿片类药治疗癌痛的疗效与基因多态性的相关性研究进展[J].中国药房,2012,23(18):1706-1707
3 李颖,李翔,罗欢,等.基因多态性对阿片类药物疼痛治疗影响的研究进展[J].中国医院药学杂志,2018,38(2):203-207
4 Ren ZY,Xu XQ,Bao YP,et al.The impact of genetic variation on sensitivity to opioid analgesics in patients with postoperative pain:a systematic review and meta-analysis[J].Pain Physician,2015,18(2):131-152
5 Hajj A,Peoc'h K,Laplanche JL,et al.Genotyping test with clinical factors:better management of acute postoperative pain?[J].Int J Mol Sci,2015,16(3):6298-6311
6 朱敏,潘志强,张璐,等.ABCB1基因多态性与癌痛感知及癌痛病人阿片需求量的关联性分析[J].中国疼痛医学杂志,2017,23(6):426-428
7 Cajanus K,Kaunisto MA,Tallgren M,et al.How much oxycodone is needed for adequate analgesia after breast cancer surgery:effect of the OPRM1 118A>G polymorphism[J].J Pain,2014,15(12):1248-1256
8 Song F,Xiong T,Parekh-Bhurke S,et al.Inconsistency between direct and indirect comparisons of competing interventions:meta-epidemiological study[J].BMJ,2011,343 :d4909
9 Stang A.Critical evaluation of the Newcastle-Ottawa scale for the assessment of the quality of nonrandomized studies in meta-analyses[J].Eur J Epidemiol,2010,25(9):603-605
10 原卫生部.癌症疼痛诊疗规范(2011年版)[J].临床肿瘤学杂志,2012,17(2):153-159
11 Klepstad P,Rakvag TT,Kaasa S,et al.The 118 A>G polymorphism in the humanμ-opioid receptor gene may increase morphine requirements in patients with pain caused by malignant disease[J].Acta Anaesthesiol Scand,2004,48(10):1232-1239
12 Gong XD,Wang JY,Liu F,et al.Gene polymorphisms of OPRM1 A118G and ABCB1 C3435T may inuence opioid requirements in Chinese patients with cancer pain[J].Asian Pac J Cancer Prev,2013,14(5):2937-2941
13 张群,王守星,黄桂春,等.OPRM1基因多态性对癌痛患者使用芬太尼透皮贴剂镇痛效应的影响[J].癌症进展,2015,13(6):615-617
14 李颖,吴飞雪,孙立,等.OPRM1 A118G多态性对我国汉族癌痛患者阿片类药物使用剂量的影响[J].中国药房,2016,27(20):2737-2738
15 李擎,刘勇,于洋,等.μ阿片受体A118G基因多态性预测盐酸羟考酮的镇痛效果[J].医药导报,2016,35(5):481-483
16 Zhang W,Yuan JJ,Kan QC,et al.Study of the OPRM1A118G genetic polymorphism associated with postoperative nausea and vomiting induced by fentanyl intravenous analgesia[J].Minerva Anesthesiol,2011,77(1):33-39
17 Zwisler ST,Enggaard TP,Noehr-jensen L,et al.The antinociceptive effect and adverse drug reactions of oxycodone in humanexperimental pain in relation to genetic variations in the OPRMIand ABCB1 genes[J].Fundam Clin Pharmacol,2010,24(4)517-524
18 Lee SH,Kim JD,Park SA,et al.Effects ofμ-Opioid receptor gene polymorphism on postoperative nausea and vomiting in patients undergoing general anesthesia with remifentanil:Double blinded randomized trial[J].J Korean Med Sci,2015,30(5):651-657
19 Hwang IC,Park JY,Myung SK,et al.OPRM1 A118G gene vatiant and postoperative opioid requirement:a systematic review and meta-analysis[J].Anesthesiology,2014,121(4):825-832
20 Chen D,Liu L,Xiao Y,et al.Ethnic-specific meta-analyses of association between the OPRM1 A118G polymorphism and alcohol dependence among Asinans and Causaians[J].Drug Alcohol Depend,2012,123(1-3):1-6
21 张双全,李少英,谭秀华.μ受体基因118A→G突变对芬太尼椎管内镇痛作用的影响[J].南方医科大学学报,2013,33(2):309-311
22 Matic M,Jongen JL,Elens L,et al.Advanced cancer pain:the search for genetic factors correlated with interindividual variability in opioid requirement[J].Pharmacogenomics,2017,18(12):1133-1142
23 Chatti I,Woillard JB,Mili A,et al.Genetic Analysis of Mu and Kappa Opioid Receptor and COMT Enzyme in Cancer Pain Tunisian Patients Under Opioid Treatment[J].Iran J Public Health,2017,46(12):1704-1711
24 Reyes-Gibby CC,Shete S,Rakvg T,et al.Exploring joint effects of genes and the clinical efficacy of morphine for cancer pain:OPRM1 and COMT gene[J].Pain,2007,130(1-2):25-30
25 Cajanus K,Kaunisto MA,Tallgren M,et al.How much oxycodone is needed for adequate analgesia after breast cancer surgery:effect of the OPRM1 118A>G polymorphism[J].J Pain,2014,15(12):1248-1256
26 Baber M,Chaudhry S,Kelly L,et al.The pharmacogenetics of codeine pain relief in the postpartum period[J].Pharmacogenomics J,2015,15(5):430-435
27 Khalil H,Sereika SM,Dai F,et al.OPRM1 and COMT gene-gene interaction is associated with postoperative pain and opioid consumption after orthopedic trauma[J].Biol Res Nurs,2017,19(2):170-179
28 Hajj A,Halepian L,Osta NE,et al.OPRM1 c 118A>G polymorphism and duration of morphine treatment associated with morerphine doses and quality-of-life in palliative cancer pain settings[J].Int J Mol Sci,2017,18(4):1-17
29 Gong XD,Wang JY,Liu F,et al.Gene polymorphis of OPRM1 A118G and ABCB1 C3435T may influence opioid requirements in Chinese patients with cancer pain[J].Asian Pac J Cancer Prev,2013,14(5):2937-2943
30 罗希,李杏莉,胡佩武,等.μ阿片受体基因多态性与美沙酮维持治疗剂量的关联分析[J].实用预防医学,2016,23(5):513-515