Sleep quality and OPRM1 polymorphisms: a cross-sectional study among opioid-naive individuals

ABSTRACT O sistema opioidérgico envolve a regulação do sono e da vigília. É possível, portanto, que os polimorfismos genéticos no OPRM1 influenciem na qualidade do sono. Este estudo investigou a associação de polimorfismos do OPRM1 com a qualidade subjetiva do sono entre indivíduos sem tratamento prévio com opióides. Este estudo observacional de corte transversal envolveu 161 homens que nunca haviam se tornado opióides (média de idade = 27,74 anos; variação: 18 a 63 anos). A qualidade subjetiva do sono foi avaliada com a versão traduzida e validada em malaio do Índice de Qualidade do Sono de Pittsburgh (PSQI). O DNA foi extraído do sangue total e submetido à reação em cadeia da polimerase (PCR) para dois polimorfismos OPRM1 (118A> G e IVS2 + 691G> C). Sujeitos combinados com 118A e IVS2 + 691Galelos (haplótipo AC) apresentaram escores significativamente mais baixos do PSQI [média (DP) = 4,29 (1,76)] em comparação àqueles sem o haplótipo [4,99 (2,50)] (p = 0,004). Por outro lado, os indivíduos com genótipo heterozigótico combinado (GC / AG diplotipo) apresentaram escores significativamente mais altos do PSQI em comparação àqueles sem o diplótipo [6,04 (2,48) vs 4,54 (2,22), p = 0,004]. Em indivíduos sem tratamento prévio com opiáceos, o haplótipo AC e o diplótipo GC / AG para os polimorfismos 118A> G e IVS2 + 691G> C do OPRM1 estão associados a uma melhor e pior qualidade do sono, respectivamente.

Association of the therapeutic efficacy and toxicity of Morphine with polymorphism of drug metabolism-related genes in the treatment of cancer pain / 中华老年医学杂志

Objective To investigate the relationship of OPRM1 C354A mutations with the clinical efficacy and toxicity of Morphine in the treatment of cancer pain.Methods We recruited 100 patients with moderate-severe cancer pain treated at our department from January 2016 to December 2016,and divided them into a CA(wild type homozygotes) group,a CG(mutated heterozygotes) group,and a GG (homozygous homozygous) group,according to the allele type of OPRM1 C354A.Regular analgesic doses of Morphine were given to all groups,and VAS scores and adverse reactions at 2,4,8,16,24,aud 48 hours after analgesia were collected and compared among the groups.Results The (OPRM1 C354A mutation groups(CG+GG)had lower VAS scores at every time point,compared with those of the non-mutation group(CA) (2 h:3.61±0.39 vs.4.04±0.52;4 h:3.88±0.41 vs.4.20± 0.15;8 h:3.95±0.32 vs.4.37±0.24;16 h:3.81±0.38 vs.4.33±0.15;24 h:3.84±0.25 vs.4.42± 0.18;and48 h:3.86±0.20 vs.4.41± 0.14) (t=4.648,5.261,7.461,8.454,13.389,and 16.030,respectively,each P=0.000).The incidences of constipation(23.08％ vs.6.25％)and vertigo(25％ vs.8.33％)in the OPRM1 C354A mutation groups(CG+GG)were significantly higher than those in the non-mutation group(CA) (x2 =5.543 and 4.914.P=0.019 and 0.027,respectively).Conclusions Polymorphism of the (PRM1 C354A gene is associated with the clinical efficacy and toxicity of morphine in the treatment of cancer pain.

Effects of OPRM1 A118G Gene Polymorphism on the Dosage of Opioids in Chinese Han Population Pa-tients with Cancer Pain / 中国药房

OBJECTIVE:To provide reference for the individualized treatment of opioid drugs by investigating the effects of OPRM1 A118G gene polymorphism on opioids dosage in Chinese Han Population patients with cancer pain. METHODS:66 Chi-nese Han Population patients with medium and severe cancer pain were selected from a third grade class A hospital. Using fluores-cence in-situ hybridization,OPRM1 A118G genotypes were detected to compare the opioids dosage of different genotype in pa-tients with cancer pain. RESULTS:Among 66 patients,distribution frequency of AA,AG and GG genotype were 36.36%, 53.03% and 10.61%,respectively;those of A and G allele were 62.88% and 37.12%;the daily dosage of opioids in AA,AG, GG genotype patients respectively were(21.67±13.41),(42.00±32.18)and(87.14±73.65)mg,with statistical significance(P<0.001). Among 39 patients receiving opioids for the first time,the dosage of 6 AA genotype patients and 15 AG genotype patients had been adjusted,with statistical significance(P=0.026). After adjusting dosage,daily dosage of AA genotype and AG genotype patients were (16.11 ± 9.16) and(28.57 ± 18.52)mg,with statistical significance (P=0.011). CONCLUSIONS:OPRM1 A118G genotype can influence the dosage of opioid in Chinese Han Population patients with cancer pain,and gene polymorphism can be used as evidence for dosage guide of opioids.

Association of single nucleotide polymorphisms of ABCB1, OPRM1 and COMT with pain perception in cancer patients / 华中科技大学学报（医学）（英德文版）

Pain perception is influenced by multiple factors. The single nucleotide polymorphisms (SNPs) of some genes were found associated with pain perception. This study aimed to examine the association of the genotypes of ABCB1 C3435T, OPRM1 A118G and COMT V108/158M (valine 108/158 methionine) with pain perception in cancer patients. We genotyped 146 cancer pain patients and 139 cancer patients without pain for ABCB1 C3435T (rs1045642), OPRM1 A118G (rs1799971) and COMT V108/158M (rs4680) by the fluorescent dye-terminator cycle sequencing method, and compared the genotype distribution between groups with different pain intensities by chi-square test and pain scores between groups with different genotypes by non-parametric test. The results showed that in these cancer patients, the frequency of variant T allele of ABCB1 C3435T was 40.5%; that of G allele of OPRM1 A118G was 38.5% and that of A allele of COMT V108/158M was 23.3%. No significant difference in the genotype distribution of ABCB1 C3435T (rs1045642) and OPRM1 A118G (rs1799971) was observed between cancer pain group and control group (P=0.364 and 0.578); however, significant difference occurred in the genotype distribution of COMT V108/158M (rs4680) between the two groups (P=0.001). And the difference could not be explained by any other confounding factors. Moreover, we found that the genotypes of COMT V108/158M and ABCB1 C3435T were associated with the intensities of pain in cancer patients. In conclusion, our results indicate that the SNPs of COMT V108/158M and ABCB1 C3435T significantly influence the pain perception in Chinese cancer patients.

Association of OPRMI and CYP3A gene polymorphisms with fentanyl analgesic effect on abdominal hysterec-tomy / 中国基层医药

Objective To discuss the influence of μ-opioid receptor ( OPRM1) and CYP3A gene polymor-phism on analgesic effect of fentanyl for abdominal hysterectomy patients .Methods 198 cases of gynecologic anes-thesia patients who were treated by elective abdominal hysterectomy surgery ,were selected in the hospital .The rela-tionship between the fentanyl consumption of intravenous analgesia and OPRMI and CYP 3A gene polymorphisms was detected by using polymerase chain reaction-restriction fragment length polymorphism detection .Results In 198 pa-tients,OPRM1 genotyping was 186 cases,the other 10 patients failed to typing were excluded ,including 89 cases of type A/A,type A/G 76 cases,type G/G 21 cases,OPRM1 the frequency of A118G allele was 31.7%.No statistically significant differences were found in mean VAS score of CYP 3A4*1/*1,CYP3A4*1/*1G,CYP3A4*1G/*1G instantly after operation in the three groups and 24h postoperation.By using analysis of variance with body mass ,age and intraoperative volume as a covariate factors after first 24h fentanyl consumption ,the difference was statistically sig-nificant among the three groups (P0.05).In addition,because the OPRM1 A118G interacts with CYP3A4*1G, reducedthe quantity of expression of opioid receptor carrying CYP 3A4*1 and OPRM1 A118G/G,and thus more fent-anyl was needed postoperation to achieve the same effect .Conclusion It provided a theoretical basis and reference for clinical application of personalized medicine by analyzing the gynecological patients μopioid receptor gene A118G and CYP3A4*1G polymorphism.