新疆维吾尔族、哈萨克族和汉族疼痛敏感性与SLC6A4基因多态性的相关性研究
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摘要
目的探讨新疆地区维吾尔族、哈萨克族和汉族疼痛敏感性与SLC6A4基因多态性间的相关性。方法随机选取2017年6月至2018年2月在新疆医科大学附属中医医院就诊接受结直肠癌根治术的维吾尔族、哈萨克族、汉族患者各50例,分别采集患者入院后空腹静脉血抽提DNA通过聚合酶链反应-限制性片段长度多态性检测技术(PCR-RFLP)对SLC6A4基因多态性位点进行检测;利用便携式压力测试仪对患者试验性疼痛压力痛阈(PPT)和耐痛阈(PTO)进行检测;术后6、12、24、48h记录患者VAS评分并统计48h内镇痛不全及不良反应发生率。结果维吾尔族高表达5-HTT基因型(18%)、中表达5-HTT基因型(70%)与低表达5-HTT基因型(12%)患者比例与哈萨克族(12%、60%、28%)、汉族(8%、58%、34%)患者差异有统计学意义(χ2=4.391,P=0.043);3组患者PPT差异无统计学意义(F=0.317,P=0.633),维吾尔族患者PTO低于哈萨克族和汉族患者,差异有统计学意义(F=2.514,P=0.047),同组患者低表达5-HTT基因型患者具有较高的PPT与PTO;术后6hVAS评分显示维吾尔族患者术后痛感高于哈萨克族和汉族患者,差异有统计学意义(F=2.270,P=0.015),同组内VAS评分显示低表达5-HTT基因型的患者在术后6、12、24、48hVAS评分均低于同组其他基因型患者,差异有统计学意义(P<0.05);3组患者术后48h不良反应发生率差异无统计学意义(χ2=0.862,P=0.298)。结论 SLC6A4基因多态性与新疆地区维吾尔族、哈萨克族和汉族疼痛敏感性相关,低表达5-HTT的基因型可提高患者疼痛耐受。
Objective To investigate the relationship between the pain sensitivity of Uygur,Kazak and Han nationality in Xinjiang and the polymorphism of SLC6 A4 gene.Methods From June 2017 to February 2018,patients of Uygur,Kazakh and Han nationality(50 cases in each group)in Traditional Chinese Medicine Hospital Affiliated to Xinjiang Medical University who received the colorectal cancer radical surgery were randomly selected as the research object.DNA was extracted from patients′fasting venous blood after admission.Polymorphic loci of SLC6 A4 gene were detected by polymerase chain reaction-restriction fragment length polymorphism(PCR-RFLP).The pressure pain threshold(PPT)and the pain tolerance domain(PTO)were detected by stress stimulation in patients with experimental pain.The VAS scoring system was used to record the postoperative scores of the patients in 6,12,24 and 48 h,and the rate of incomplete analgesia and the incidence of adverse reactions in patients within 48 hwas also recorded.Results The proportion of Uygur patients with high expression 5 HTT genotype(18%),moderate expression 5 HTT genotype(70%)and low expression 5 HTT genotype(12%)was significantly different from Kazakh patients(12%,60%,28%)and Han patients(8%,58%,34%)(χ2=4.391,P=0.043).There was no significant difference in PPT among three groups(F=0.317,P=0.633).The PTO of Uygur patients were lower than that of Kazak and Han patients(F=2.514,P=0.047),and in each group,the patients with low expression of 5-HTT had higher PPT and PTO levels.The VAS scores of the Uygur patients in 6 hafter operation were higher than those of the Kazakh and Han patients(F=2.270,P=0.015),and the VAS scores of patients with low expression of 5-HTT were significant lower than other genotypes in each group,and the differences were statistically significant(P<0.05).However,there was no significant difference in the incidence of adverse reactions among the 3 groups(χ2=0.862,P=0.298).Conclusion SLC6 A4 gene polymorphism is associated with pain sensitivity of Uygur,Kazak and Han nationality,and the reduced expression of 5-HTT may improve patients pain tolerance.
Objective To investigate the relationship between the pain sensitivity of Uygur,Kazak and Han nationality in Xinjiang and the polymorphism of SLC6 A4 gene.Methods From June 2017 to February 2018,patients of Uygur,Kazakh and Han nationality(50 cases in each group)in Traditional Chinese Medicine Hospital Affiliated to Xinjiang Medical University who received the colorectal cancer radical surgery were randomly selected as the research object.DNA was extracted from patients′fasting venous blood after admission.Polymorphic loci of SLC6 A4 gene were detected by polymerase chain reaction-restriction fragment length polymorphism(PCR-RFLP).The pressure pain threshold(PPT)and the pain tolerance domain(PTO)were detected by stress stimulation in patients with experimental pain.The VAS scoring system was used to record the postoperative scores of the patients in 6,12,24 and 48 h,and the rate of incomplete analgesia and the incidence of adverse reactions in patients within 48 hwas also recorded.Results The proportion of Uygur patients with high expression 5 HTT genotype(18%),moderate expression 5 HTT genotype(70%)and low expression 5 HTT genotype(12%)was significantly different from Kazakh patients(12%,60%,28%)and Han patients(8%,58%,34%)(χ2=4.391,P=0.043).There was no significant difference in PPT among three groups(F=0.317,P=0.633).The PTO of Uygur patients were lower than that of Kazak and Han patients(F=2.514,P=0.047),and in each group,the patients with low expression of 5-HTT had higher PPT and PTO levels.The VAS scores of the Uygur patients in 6 hafter operation were higher than those of the Kazakh and Han patients(F=2.270,P=0.015),and the VAS scores of patients with low expression of 5-HTT were significant lower than other genotypes in each group,and the differences were statistically significant(P<0.05).However,there was no significant difference in the incidence of adverse reactions among the 3 groups(χ2=0.862,P=0.298).Conclusion SLC6 A4 gene polymorphism is associated with pain sensitivity of Uygur,Kazak and Han nationality,and the reduced expression of 5-HTT may improve patients pain tolerance.
引文
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[17]ARENDT-NIELSEN L,PEDERSEN P,POULSEN L,et al.A 5-HT Antagonist(UP 26-91)versus Codeine and Placebo in a Human Experimental Pain Study[J].Pain Res Manag,2016,5(2):135-140.
[18]XU Z F,YANG B,ZHANG J H,et al.The regulation of sGC on the rat model of neuropathic pain is mediated by5-HT1ARs and NO/cGMP pathway[J].Am J Transl Res,2016,8(2):1027-1036.
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[3]柯雪茹,雷波,王明春,等.新疆维吾尔族与哈萨克族和汉族患者疼痛敏感性及舒芬太尼镇痛剂量的比较研究[J].中国全科医学,2016,19(8):916-919.
[4]刘艳,于生元.5-HT_(2c)受体基因Cys23Ser多态性与偏头痛关系的临床研究[J].中国疼痛医学杂志,2010,16(1):3-5.
[5] AL E.A 5-HT antagonist(UP 26-91)versus codeine and placebo in a human experimental pain study,Pulsus Group Inc[J].2016,5(2):135-140.
[6]谢在宏,潘广达,景东望,等.局部麻醉药硬膜外腔持续输注的临床研究[J].中国临床医生,2014,42(5):66-67.
[7]魏鸿,王灿.腹腔镜下结直肠全系膜切除术与传统开腹手术对结直肠癌患者的免疫功能及预后比较[J].医学综述,2016,22(17):3462-3465.
[8]王向阳,赵晶,张伟,等.右美托咪定联合舒芬太尼用于术后镇痛对宫颈癌根治术患者心血管稳定性及VAS评分的影响[J].中国妇幼健康研究,2017,28(5):606-608.
[9] BLAZEVIC S,HORVATICEK M,KESIC M,et al.Epigenetic adaptation of the placental serotonin transporter gene(SLC6A4)to gestational diabetes mellitus[J].PLoS One,2017,12(6):e0179934.
[10]CORDER G,TAWFIK V L,WANG D,et al.Loss ofμ-opioid receptor signaling in nociceptors,and not spinal microglia,abrogates morphine tolerance without disrupting analgesic efficacy[J].Nat Med,2017,23(2):164-173.
[11]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,2018,12(2):203-208.
[12]秦永章,肖丽霞,柯瑞琼,等.5-HTTLPR基因多态性与糖尿病周围神经性疼痛疗效的关系[J].中国当代医药,2016,23(32):44-46.
[13]SJAARDA C P,HECHT P,MCNAUGHTON A J,et al.Interplay between maternal Slc6a4mutation and prenatal stress:apossible mechanism for autistic behavior development[J].Sci Rep,2017,7(1):8735.
[14]GRUENBLATT E,MARINOVA Z,ROTH A,et al.Combining genetic and epigenetic parameters of the serotonin transporter gene in obsessive-compulsive disorder[J].J Psychiatr Res,2018,96(4):209-217.
[15]LOGGIA M L,JENSEN K,GOLLUB R L,et al.The Catechol-O-Methyltransferase(COMT)val(158)Met polymorphism affects brain responses to repeated painful stimuli[J].PLoS One,2011,6(11):e27764.
[16]肖智,文松.中脑导水管周围灰质5-HT_7受体在神经病理性疼痛中的镇痛作用研究[J].中国疼痛医学杂志,2014,20(12):861-865.
[17]ARENDT-NIELSEN L,PEDERSEN P,POULSEN L,et al.A 5-HT Antagonist(UP 26-91)versus Codeine and Placebo in a Human Experimental Pain Study[J].Pain Res Manag,2016,5(2):135-140.
[18]XU Z F,YANG B,ZHANG J H,et al.The regulation of sGC on the rat model of neuropathic pain is mediated by5-HT1ARs and NO/cGMP pathway[J].Am J Transl Res,2016,8(2):1027-1036.
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