COMTvall58met和OPRM1A118G基因多态性对国人电刺激疼痛敏感性和术前焦虑的影响
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摘要
[目的与背景]
疼痛和术前焦虑状态是现代麻醉工作必须面临和禀待解决的问题。严重影响到患者对临床治疗的配合和围手术期的顺利渡过。随着人们生活水平不断的提高和对自身生活质量的重视,对医疗服务提出了更高的要求。现代高品质的医疗服务提倡人性化和个体化服务。所以,深入研究疼痛感知和术前焦虑状态的基因学背景十分必要。也是人性化服务和个体化治疗的必然趋势。
疼痛治疗是临床麻醉工作的一个重要方面。人类对疼痛敏感性存在明显的个体差异,导致这种个体差异的因素很多,如：以前疼痛经历、性格、性别、及遗传背景等。但是,至少这种差异部分是遗传学背景的造成的。
随着对基因研究的深入,对疼痛的研究更多地开始从基因角度考虑,而且越来越多可能与疼痛相关的基因被发现和验证。特别是从2003年人类基因组计划完成后,有关治疗药物与相应疾病的遗传标记和表型变异性研究被广泛开展。人类基因组计划揭开了几乎全部的人类基因序列,这也为疼痛的基因研究创造了可能性。大量参与疼痛形成的分子介质被提上研究日程：如炎症介质(5-羟色胺、组织胺、缓激肽和细胞因子等)、第二信使、受体和内源性神经递质等。人们可以据此在不同层面上研究影响疼痛感知、疼痛敏感性和疼痛状态的基因基础。也能据此开拓和发展新的基因治疗方法和药物等。在不久的将来,有望能为疼痛的个体化治疗提供策略。
术前焦虑状态是每个面临手术的患者或多或少都会经历的,也是临床医生所关注的棘手难题。疼痛和围手术期的焦虑两者关系密切。疼痛本身就会引起患者极度不适和精神焦虑。反之,围手术期的紧张和焦虑也会改变疼痛的感知。一些平时轻微的疼痛,在焦虑状态时,疼痛刺激可能会被放大或夸大。同时,除社会、心理因素外,两者都受遗传因素影响,甚至被遗传因素所决定。而两者又有很多共同的基因背景和遗传联系。所以对二者的联合研究具有重要意义。
本研究拟选择被大家广泛认可的与疼痛和精神神经因素相关的COMTval158met和OPRM1A118G基因多态性,首次探讨其对疼痛敏感性和术前焦虑的影响。以期为后续研究和临床工作提供一些有价值的信息和参考。
[材料与方法]
1.研究对象284例择期手术患者和28例健康志愿者,年龄20-50岁,体重指数(BMI)在正常范围(1±20%),美国麻醉医师协会ASA分级Ⅰ或Ⅱ级。排除标准：有慢性疼痛史、使用镇痛药物的患者,有酗酒、吸烟史、糖尿病、肝脏病、肾脏病、心血管疾病史的患者,有精神神经疾病史的患者。所有患者经医院伦理委员会同意并签署知情同意书后进入试验。
2.疼痛敏感性测量和焦虑状态评分使用电刺激仪进行测痛,并让患者熟悉测定的整个过程,使其能准确区分痛阈和耐痛阈。重复测定3次痛阈和耐痛阈,各取其平均值。所有患者术前接受特质焦虑状态问卷调查评分,记录焦虑评分(SAI评分)和特质评分(TAI评分)。
3.基因多态性检测外周静脉留置针采集静脉血5ml,提取基因组DNA；采用聚合酶链反应-限制性片段长度多态性分析(PCR-RFLP)技术,对COMTval158met和OPRM1A118G多态性位点进行检测分析。通过直接对PCR扩增产物进行测序以验证基因型检测结果的可靠性。
4.统计学分析统计学分析采用SPSS12.0软件进行,计量资料以x±s(均数±标准差)表示,等位基因和基因型分布是否符合Hardy-Weinberg平衡采用χ2检验进行检测；对多组计量数据进行单因素方差分析(ANOVA),各组间比较采用LSD法。不同基因型组间痛阈、耐痛阈、SAI和TAI评分比较采用协方差分析以排除其它影响因素。采用spearman等级相关分析突变等位基因与痛阈、耐痛阈、SAI和TAI评分之间的相关性。以P<0.05作为差别有统计学意义的检验标准。
[结果]
1.一般情况
284例患者中,平均年龄为38.8±9.5岁(21-50),体重指数(BMI)为18.4±2.5kg/m2。28例健康志愿者平均年龄为22.4±2.1岁(18-25),体重指数(BMI)为15.6±2.7kg/m2。所有患者和健康志愿者一般情况比较无差异(P＞0.05)。
2.国内人群中COMTval158met和OPRM1A118G多态性等位基因突变率
COMTvall58met和OPRM1A118G等位基因在国内人群中的突变率分别为34.2%和32.1%。等位基因和基因型分布符合Hardy-weinberg平衡。
3.COMTval158met基因多态性对患者疼痛敏感性和术前焦虑的影响
按COMTvall58met基因型进行分组,患者一般情况比较三组之间差异无统计学意义(P>0.05)；三组之间耐痛阈和痛阈比较差异有统计学意义(P＜0.05),met/met(1.6±0.9mA,4.5±1.1mA)组低于val/val组(2.2±0.7mA,5.4±.2mA),val/val组与val/met组无差异。术前焦虑状态评分(SAI和TAI)met/met组(51.5±10.8,49.2±10.0)高于val/val组(44.4±9.5,43.1±7.3),val/val组与val/met组无差异(P＞0.05)。与健康志愿者比较,术前焦虑评分(SAI)升高,特质评分(TAI)无差异(P＞0.05),痛阈和耐痛阂均降低(P＜0.05)。
4. COMTval158met和OPRM1A118G基因多态性对患者疼痛敏感性和术前焦虑
的联合影响
联合基因分型成功277例,按OPRM1A118G和COMTvall58met基因型联合分组后,九组之间一般情况比较差异无统计学意义(P＞0.05)；相对于中性的A/G并val/met组,G/G并val/met组和G/G并met/met组痛阈降低；G/G并val/val组、G/G并val/met组和G/G并met/met组耐痛阈降低(P＜0.05)。相对于中性的A/G并val/met组,术前焦虑状态评分SAI和TAI在A/G并met/met组和G/G并met/met组升高(P＜0.05)。
[结论]
1. COMTval158met基因多态性是术前焦虑的易感因素。相对野生型纯合子和杂
合子,携带met158met等位基因的个体更容易术前焦虑。
2.在疼痛敏感性方面,COMTval158met和OPRM1A118G基因多态性有协同作用,COMT基因met158met多态性加重患者术前焦虑,间接影响患者疼痛敏感性,使疼痛敏感性增强；痛阈和耐痛阈相应降低。
3.相对于COMTval158met, OPRM1A118G基因多态性是影响机体疼痛敏感性的主要因素。118G多态性提高患者疼痛敏感性,使患者痛阈、耐痛阈降低。
4. OPRM1A118G基因多态性对患者术前焦虑无影响。
Background and Objective
Pain and preoperative anxiety are serious problem that we have to be faced with clinical anesthesia, and which will affect therapy smoothly of perioperative. Adequate release of pain and anxiety are necessary before and after operation to decrease the incidence of complication. As that to be considered, much things should be done with this.
Since the completion of the Human Genome project in2003, there has been an increasing trend in medicine to correlate disease to genetic markers and phenotypic variance. The Human Genome Project revealed nearly complete genomic sequence data which provide the basis for further research on genomic variations influencing nociception, susceptibility to pain conditions, as well as response to pharmacotherapy. Polymorphisms of receptors, transporters, metabolizing enzymes, and other targets of pharmacotherapy and the nociceptive system are currently under investigation. Molecular mediators of pain processing such as inflammatory mediators (serotonin, histamine, bradykinin and cytokines), second messengers, receptors and endogenous neurotransmitters are under investigation, and will hopefully reveal new strategies for individualized pain management in the future.
An individualized profile for patients at risk for severe pain or anxiety disorders, and a pharmacotherapy considering the patients'genetic background might considerably improve pain and anxiety disorders management.
Research in the field of pain and anxiety management has revealed various genomic variations influencing sensitivity to pain, susceptibility to anxiety disorders. Future developments have to focus on the translation of these findings into clinical practice. Multiple genes are involved and single genes only have small contributions to the overall genetic impact. Up to now, however, most studies have addressed only one or a few single gene variations. The complexity of these genetic disorders still has to be elucidated.
Our research aims the commonly candidate genetic polymorphism to determine the frequencies of COMTval158met and OPRM1A118G alleles in Chinese patients and to observe the associated impact of COMTval158met and OPRM1A118G on pain sensitivity and preoperative anxiety. The present study seem to provides an important foundation and theoretical evidence for the gene-directed treatment of pain and preoperative anxiety.
Materials and Methods
Subjects
Two hundred and eighty-four patients and twenty-eight healthy volunteers, aged20-50yr, within±20%of ideal body weight, and having an American Society of Anesthesiologists (ASA) physical status of I or II, undergoing selective operation were enrolled. Exclusion criteria included the following:known history of psychiatric disease, nervous disease, significant cardiovascular disease, hepatic or renal dysfunction, diabetes mellitus, alcohol or drug abuse, chronic analgesic use, pregnancy or nursing. All patients were of Chinese Han nationality and live in Henan province of China. The study design was approved by Institutional Ethics Committee of Zhengzhou University.
Measurement of pain sensitivity and score of anxiety state
Preoperatively, the pain threshold and pain tolerance threshold were measured three times using electrical stimulation and to recorded the average number. All patients to be enrolled in the trial accepted the investigation of anxiety state and recorded the score of SAI and TAI.
Genotyping assays
Venous blood samples (5ml) were collected from all patients in this study. DNA was extracted from leukocytes using a standard phenol/chloroform procedure. Genotyping of COMTval158met and OPRM1A118G alleles was conducted by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP).
Statistical analysis
SPSS12.0software was used for statistical analyses. Chi-square test was used to verify Hardy-Weinberg equilibrium. Data for the pain threshold, pain tolerance threshold, SAI and TAI score were compared among the genotype group using one-way analysis of variance with covariance analysis correction for multiple comparisons was performed before and after adjusted for age and weight. P-values <0.05were considered with statistically significant.
Results General information
Among the two hundred and eighty-four subjects, the mean of age was38.8years, and the mean of body mass index was18.4. Among the twenty-eight healthy volunteers, correspondingly, the mean of age was22.4years, and the mean of body mass index was15.6. There was no significant difference between patients and volunteers in general information except the age.
Frequencies of OPRM1A118G and COMTval158met
The frequencies of COMTval158met and OPRM1A118G alleles in Chinese patients were0.342and0.321, respectively. The allele frequencies were in Hardy-Weinberg equilibrium.
Effects of COMTval158met genetic polymorphism on pain sensitivity and preoperative anxiety
There was no significant differences in general information among the three genotype groups. PT and PTT were statistical different between met/met (1.6±0.9mA,4.5±1.1mA) and val/val (2.2±0.7mA,5.4±1.2mA) groups (P<0.05), SAI and TAI score were statistical different also between met/met (51.5±10.8,49.2±10.0) and val/val (44.4±9.5,43.1±7.3) groups (P<0.05), and there were no significant difference between val/val and val/met groups in PT, PTT, SAI and TAI score. However, compared with healthy volunteers'groups correspondingly, there were significantly lower in PT and PTT, and significantly higher in SAI score(P<0.05). There was no significant difference in TAI score(P>0.05).
Association effects of COMTvall58met and OPRM1A118G genetic polymorphism on pain sensitivity and preoperative anxiety
There were twe hundreds and seventy-seven patients had carried out succeed in the joint genotyping. After association studied the COMTval158met and OPRM1A118G genetic polymorphism, they were divided into nine groups. Group A/A and val/val(n=68), group A/A and val/met(n=50), group A/A and met/met(n=17), group A/G and val/val(n=43), group A/G and val/met(n=46), group A/G and met/met(n=17), group G/G and val/val(n=18), group G/G and val/met(n=10), and group G/G and met/met(n=8). There was no significant differences in general information among the nine genotype groups. According to the neutral group A/G and val/met, there was significantly lower in PT at group G/G and val/met, and group G/G and met/met; there was significantly lower in PTT at group G/G and val/val, group G/G and val/met, and group G/G and met/met(P<0.05); there were significantly higher in SAI and TAI score at group A/G and met/met, and group G/G and met/met (P<0.05).
Conclusions
1. The COMTvall58met genetic polymorphism is a predisposing factor of preoperative anxiety. Compare with val158val and val158met, the patients with met158met genotype have the more probability in preoperative anxiety state.
2. The COMTval158met genetic polymorphism would exacerbate the preoperative anxiety, and at the same time enhance pain sensitivity, through the remote effects on pain sensitivity.
3. The OPRM1A118G genetic polymorphism is the main factor which affect pain sensitivity, the gene mutation of118G will enhance pain sensitivity and decrease the PT and PTT.
4. There is no significantly relationship between the OPRM1A118G genetic polymorphism and preoperative anxiety.
疼痛和术前焦虑状态是现代麻醉工作必须面临和禀待解决的问题。严重影响到患者对临床治疗的配合和围手术期的顺利渡过。随着人们生活水平不断的提高和对自身生活质量的重视,对医疗服务提出了更高的要求。现代高品质的医疗服务提倡人性化和个体化服务。所以,深入研究疼痛感知和术前焦虑状态的基因学背景十分必要。也是人性化服务和个体化治疗的必然趋势。
疼痛治疗是临床麻醉工作的一个重要方面。人类对疼痛敏感性存在明显的个体差异,导致这种个体差异的因素很多,如：以前疼痛经历、性格、性别、及遗传背景等。但是,至少这种差异部分是遗传学背景的造成的。
随着对基因研究的深入,对疼痛的研究更多地开始从基因角度考虑,而且越来越多可能与疼痛相关的基因被发现和验证。特别是从2003年人类基因组计划完成后,有关治疗药物与相应疾病的遗传标记和表型变异性研究被广泛开展。人类基因组计划揭开了几乎全部的人类基因序列,这也为疼痛的基因研究创造了可能性。大量参与疼痛形成的分子介质被提上研究日程：如炎症介质(5-羟色胺、组织胺、缓激肽和细胞因子等)、第二信使、受体和内源性神经递质等。人们可以据此在不同层面上研究影响疼痛感知、疼痛敏感性和疼痛状态的基因基础。也能据此开拓和发展新的基因治疗方法和药物等。在不久的将来,有望能为疼痛的个体化治疗提供策略。
术前焦虑状态是每个面临手术的患者或多或少都会经历的,也是临床医生所关注的棘手难题。疼痛和围手术期的焦虑两者关系密切。疼痛本身就会引起患者极度不适和精神焦虑。反之,围手术期的紧张和焦虑也会改变疼痛的感知。一些平时轻微的疼痛,在焦虑状态时,疼痛刺激可能会被放大或夸大。同时,除社会、心理因素外,两者都受遗传因素影响,甚至被遗传因素所决定。而两者又有很多共同的基因背景和遗传联系。所以对二者的联合研究具有重要意义。
本研究拟选择被大家广泛认可的与疼痛和精神神经因素相关的COMTval158met和OPRM1A118G基因多态性,首次探讨其对疼痛敏感性和术前焦虑的影响。以期为后续研究和临床工作提供一些有价值的信息和参考。
[材料与方法]
1.研究对象284例择期手术患者和28例健康志愿者,年龄20-50岁,体重指数(BMI)在正常范围(1±20%),美国麻醉医师协会ASA分级Ⅰ或Ⅱ级。排除标准：有慢性疼痛史、使用镇痛药物的患者,有酗酒、吸烟史、糖尿病、肝脏病、肾脏病、心血管疾病史的患者,有精神神经疾病史的患者。所有患者经医院伦理委员会同意并签署知情同意书后进入试验。
2.疼痛敏感性测量和焦虑状态评分使用电刺激仪进行测痛,并让患者熟悉测定的整个过程,使其能准确区分痛阈和耐痛阈。重复测定3次痛阈和耐痛阈,各取其平均值。所有患者术前接受特质焦虑状态问卷调查评分,记录焦虑评分(SAI评分)和特质评分(TAI评分)。
3.基因多态性检测外周静脉留置针采集静脉血5ml,提取基因组DNA；采用聚合酶链反应-限制性片段长度多态性分析(PCR-RFLP)技术,对COMTval158met和OPRM1A118G多态性位点进行检测分析。通过直接对PCR扩增产物进行测序以验证基因型检测结果的可靠性。
4.统计学分析统计学分析采用SPSS12.0软件进行,计量资料以x±s(均数±标准差)表示,等位基因和基因型分布是否符合Hardy-Weinberg平衡采用χ2检验进行检测；对多组计量数据进行单因素方差分析(ANOVA),各组间比较采用LSD法。不同基因型组间痛阈、耐痛阈、SAI和TAI评分比较采用协方差分析以排除其它影响因素。采用spearman等级相关分析突变等位基因与痛阈、耐痛阈、SAI和TAI评分之间的相关性。以P<0.05作为差别有统计学意义的检验标准。
[结果]
1.一般情况
284例患者中,平均年龄为38.8±9.5岁(21-50),体重指数(BMI)为18.4±2.5kg/m2。28例健康志愿者平均年龄为22.4±2.1岁(18-25),体重指数(BMI)为15.6±2.7kg/m2。所有患者和健康志愿者一般情况比较无差异(P＞0.05)。
2.国内人群中COMTval158met和OPRM1A118G多态性等位基因突变率
COMTvall58met和OPRM1A118G等位基因在国内人群中的突变率分别为34.2%和32.1%。等位基因和基因型分布符合Hardy-weinberg平衡。
3.COMTval158met基因多态性对患者疼痛敏感性和术前焦虑的影响
按COMTvall58met基因型进行分组,患者一般情况比较三组之间差异无统计学意义(P>0.05)；三组之间耐痛阈和痛阈比较差异有统计学意义(P＜0.05),met/met(1.6±0.9mA,4.5±1.1mA)组低于val/val组(2.2±0.7mA,5.4±.2mA),val/val组与val/met组无差异。术前焦虑状态评分(SAI和TAI)met/met组(51.5±10.8,49.2±10.0)高于val/val组(44.4±9.5,43.1±7.3),val/val组与val/met组无差异(P＞0.05)。与健康志愿者比较,术前焦虑评分(SAI)升高,特质评分(TAI)无差异(P＞0.05),痛阈和耐痛阂均降低(P＜0.05)。
4. COMTval158met和OPRM1A118G基因多态性对患者疼痛敏感性和术前焦虑
的联合影响
联合基因分型成功277例,按OPRM1A118G和COMTvall58met基因型联合分组后,九组之间一般情况比较差异无统计学意义(P＞0.05)；相对于中性的A/G并val/met组,G/G并val/met组和G/G并met/met组痛阈降低；G/G并val/val组、G/G并val/met组和G/G并met/met组耐痛阈降低(P＜0.05)。相对于中性的A/G并val/met组,术前焦虑状态评分SAI和TAI在A/G并met/met组和G/G并met/met组升高(P＜0.05)。
[结论]
1. COMTval158met基因多态性是术前焦虑的易感因素。相对野生型纯合子和杂
合子,携带met158met等位基因的个体更容易术前焦虑。
2.在疼痛敏感性方面,COMTval158met和OPRM1A118G基因多态性有协同作用,COMT基因met158met多态性加重患者术前焦虑,间接影响患者疼痛敏感性,使疼痛敏感性增强；痛阈和耐痛阈相应降低。
3.相对于COMTval158met, OPRM1A118G基因多态性是影响机体疼痛敏感性的主要因素。118G多态性提高患者疼痛敏感性,使患者痛阈、耐痛阈降低。
4. OPRM1A118G基因多态性对患者术前焦虑无影响。
Background and Objective
Pain and preoperative anxiety are serious problem that we have to be faced with clinical anesthesia, and which will affect therapy smoothly of perioperative. Adequate release of pain and anxiety are necessary before and after operation to decrease the incidence of complication. As that to be considered, much things should be done with this.
Since the completion of the Human Genome project in2003, there has been an increasing trend in medicine to correlate disease to genetic markers and phenotypic variance. The Human Genome Project revealed nearly complete genomic sequence data which provide the basis for further research on genomic variations influencing nociception, susceptibility to pain conditions, as well as response to pharmacotherapy. Polymorphisms of receptors, transporters, metabolizing enzymes, and other targets of pharmacotherapy and the nociceptive system are currently under investigation. Molecular mediators of pain processing such as inflammatory mediators (serotonin, histamine, bradykinin and cytokines), second messengers, receptors and endogenous neurotransmitters are under investigation, and will hopefully reveal new strategies for individualized pain management in the future.
An individualized profile for patients at risk for severe pain or anxiety disorders, and a pharmacotherapy considering the patients'genetic background might considerably improve pain and anxiety disorders management.
Research in the field of pain and anxiety management has revealed various genomic variations influencing sensitivity to pain, susceptibility to anxiety disorders. Future developments have to focus on the translation of these findings into clinical practice. Multiple genes are involved and single genes only have small contributions to the overall genetic impact. Up to now, however, most studies have addressed only one or a few single gene variations. The complexity of these genetic disorders still has to be elucidated.
Our research aims the commonly candidate genetic polymorphism to determine the frequencies of COMTval158met and OPRM1A118G alleles in Chinese patients and to observe the associated impact of COMTval158met and OPRM1A118G on pain sensitivity and preoperative anxiety. The present study seem to provides an important foundation and theoretical evidence for the gene-directed treatment of pain and preoperative anxiety.
Materials and Methods
Subjects
Two hundred and eighty-four patients and twenty-eight healthy volunteers, aged20-50yr, within±20%of ideal body weight, and having an American Society of Anesthesiologists (ASA) physical status of I or II, undergoing selective operation were enrolled. Exclusion criteria included the following:known history of psychiatric disease, nervous disease, significant cardiovascular disease, hepatic or renal dysfunction, diabetes mellitus, alcohol or drug abuse, chronic analgesic use, pregnancy or nursing. All patients were of Chinese Han nationality and live in Henan province of China. The study design was approved by Institutional Ethics Committee of Zhengzhou University.
Measurement of pain sensitivity and score of anxiety state
Preoperatively, the pain threshold and pain tolerance threshold were measured three times using electrical stimulation and to recorded the average number. All patients to be enrolled in the trial accepted the investigation of anxiety state and recorded the score of SAI and TAI.
Genotyping assays
Venous blood samples (5ml) were collected from all patients in this study. DNA was extracted from leukocytes using a standard phenol/chloroform procedure. Genotyping of COMTval158met and OPRM1A118G alleles was conducted by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP).
Statistical analysis
SPSS12.0software was used for statistical analyses. Chi-square test was used to verify Hardy-Weinberg equilibrium. Data for the pain threshold, pain tolerance threshold, SAI and TAI score were compared among the genotype group using one-way analysis of variance with covariance analysis correction for multiple comparisons was performed before and after adjusted for age and weight. P-values <0.05were considered with statistically significant.
Results General information
Among the two hundred and eighty-four subjects, the mean of age was38.8years, and the mean of body mass index was18.4. Among the twenty-eight healthy volunteers, correspondingly, the mean of age was22.4years, and the mean of body mass index was15.6. There was no significant difference between patients and volunteers in general information except the age.
Frequencies of OPRM1A118G and COMTval158met
The frequencies of COMTval158met and OPRM1A118G alleles in Chinese patients were0.342and0.321, respectively. The allele frequencies were in Hardy-Weinberg equilibrium.
Effects of COMTval158met genetic polymorphism on pain sensitivity and preoperative anxiety
There was no significant differences in general information among the three genotype groups. PT and PTT were statistical different between met/met (1.6±0.9mA,4.5±1.1mA) and val/val (2.2±0.7mA,5.4±1.2mA) groups (P<0.05), SAI and TAI score were statistical different also between met/met (51.5±10.8,49.2±10.0) and val/val (44.4±9.5,43.1±7.3) groups (P<0.05), and there were no significant difference between val/val and val/met groups in PT, PTT, SAI and TAI score. However, compared with healthy volunteers'groups correspondingly, there were significantly lower in PT and PTT, and significantly higher in SAI score(P<0.05). There was no significant difference in TAI score(P>0.05).
Association effects of COMTvall58met and OPRM1A118G genetic polymorphism on pain sensitivity and preoperative anxiety
There were twe hundreds and seventy-seven patients had carried out succeed in the joint genotyping. After association studied the COMTval158met and OPRM1A118G genetic polymorphism, they were divided into nine groups. Group A/A and val/val(n=68), group A/A and val/met(n=50), group A/A and met/met(n=17), group A/G and val/val(n=43), group A/G and val/met(n=46), group A/G and met/met(n=17), group G/G and val/val(n=18), group G/G and val/met(n=10), and group G/G and met/met(n=8). There was no significant differences in general information among the nine genotype groups. According to the neutral group A/G and val/met, there was significantly lower in PT at group G/G and val/met, and group G/G and met/met; there was significantly lower in PTT at group G/G and val/val, group G/G and val/met, and group G/G and met/met(P<0.05); there were significantly higher in SAI and TAI score at group A/G and met/met, and group G/G and met/met (P<0.05).
Conclusions
1. The COMTvall58met genetic polymorphism is a predisposing factor of preoperative anxiety. Compare with val158val and val158met, the patients with met158met genotype have the more probability in preoperative anxiety state.
2. The COMTval158met genetic polymorphism would exacerbate the preoperative anxiety, and at the same time enhance pain sensitivity, through the remote effects on pain sensitivity.
3. The OPRM1A118G genetic polymorphism is the main factor which affect pain sensitivity, the gene mutation of118G will enhance pain sensitivity and decrease the PT and PTT.
4. There is no significantly relationship between the OPRM1A118G genetic polymorphism and preoperative anxiety.
引文
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