COMT、MTHFR基因多态性与抗精神病药导致代谢异常的关联性研究
发布时间：2018-08-07 14:46
【摘要】：目的:非典型抗精神病药物导致的体重增加及糖,脂代谢异常已经成为现今临床治疗中面临的严峻问题,这些都与心血管疾病、中风、糖尿病等疾病密切相关,大大增加了精神障碍患者的致残率和致死率。其中,遗传因素与之有密切相关,儿茶酚氧位甲基转移酶(COMT)参与调节前额叶皮质的多巴胺功能,其缺失与神经功能失调密切相关,COMT基因也是精神分裂症的易感基因;甲基化酶如亚甲基四氢叶酸还原酶(MTHFR)参与调节DNA甲基化,包括COMT的代谢产物及其它化合物发生的甲基化过程,MTHFR基因的缺陷将导致机体多个基础生化过程的紊乱。综上,COMT和MTHFR基因可能参与了抗精神病药导致代谢异常的过程,本研究分别选取这两个基因上的多态性位点:COMT(rs4680)和MTHFR(rs1801133),以期探究候选位点与抗精神病药导致的代谢变化之间的关系。方法:依据入组排除标准共纳入355例患者,所有患者接受单一非典型抗精神病药物治疗。动态观察12周,定期测量体重和腰腹围,进一步计算体质指数(BMI),同时抽取外周静脉血,检测血脂、血糖相关指标;采用高盐法抽提样本DNA,以机制铺助激光解吸电离飞行时间质谱(MALDI-TOF-MS)进行COMT(rs4680)和MTHFR(rs1801133)基因分型。不同基因型治疗前后数据比较采用独立样本t检验比较组间指数及代谢变化情况,采用方差分析比较代谢指标与基因型之间的相关性。结果:1.在全部患者中,体重增加组共有155例,体重未增加组共有200例,两组在年龄分布上可见有统计学意义(t=3.254,P0.05)。其中首发88例(24.8%),体重增加有48例(31.0%),体重未增加有40例(20.0%),两组差异有统计学意义(χ2=5.634,P0.05)。经药物治疗之后发展为代谢综合症的患者共有126例,在年龄分布上,可见发生代谢综合症(MetS)的年龄是41.02±11.27岁,未发生Met S的年龄是37.55±11.38岁,两组差异有统计学意义(P0.05)。2.在治疗前基线水平,体重增加组与体重未增加组在指标FPG、T3和T4差异有统计学意义(P均0.05)。相比于体重未增加组,体重增加组在经过单一药物治疗后,在8周末和12周末,在体重、BMI及腰围上均显著增加(P均0.05),TG、LDL和CHOL均显著增加(P均0.05)。3.比较不同抗精神病药物,发现奥氮平组体重增加最多,其次是喹硫平组,最后是利培酮组。比较三组的体重,腰围,BMI,LDL及CHOL的变化,均有统计学意义(P均0.05)。4.COMT基因rs4680位点基因型及等位基因频率在体重增加组与体重未增加组之间的分布差异均无统计学意义(P0.05),在男性和女性中的分布均无统计学意义(P0.05)。COMT基因rs4680位点基因型及等位基因频率在发生Mets与否的基因型频率分布和等位基因频率分布差异均无统计学意义(P0.05),在男性和女性中的分布均无统计学意义(P0.05)。5.MTHFR基因(rs1801133)的GG、GA、AA三种基因型在△LDL和△CHOL有统计学意义(P0.05)。6.MTHFR基因rs1801133位点基因型及等位基因频率在体重增加组与体重未增加组之间的基因型频率分布和等位基因频率分布差异均无统计学意义(P0.05),在男性和女性中的分布均无统计学意义(P0.05)。MTHFR基因rs1801133位点基因型及等位基因频率在发生Mets与否的分布差异均无统计学意义(P0.05),男性和女性中的分布均无统计学意义(P0.05)。结论:1.非典型抗精神病药物能引起明显的体重增加,首发患者及年轻患者更易发生体重增加。提示面对首发及年轻患者时,更应慎重选择抗精神病药物。2.不同非典型抗精神病药物导致的体重变化及代谢指标的变化有显著差异,其中奥氮平组体重增加最高,其次是喹硫平组,最后是利培酮组。比较三组在体重,腰围,BMI,LDL及CHOL的差异均有统计学意义。说明三种药物不仅对体重有明显影响,对代谢指标也有显著影响。3.经单一抗精神病药物治疗后,体重增加组的除体重外,BMI及腰围也比体重未增加组显著增加,代谢指标TG、LDL和CHOL均显著增加,差异有统计学意义。说明对体重增加的情况,对于代谢指标的异常也应给予高度关注。4.COMT(rs4680)不同基因型在抗精神病药物是否导致代谢综合症及体重增加不同组间的分布差异无统计学意义,且在男性和女性中的分布均无统计学意义。说明COMT(rs4680)与抗精神病药物导致代谢异常无相关性。5.MTHFR(rs1801133)不同基因型在服药后LDL和CHOL不同变化组间的差异有统计学意义,说明GG不同基因型可能与LDL和CHOL代谢相关。
[Abstract]:Objective: the weight gain of atypical antipsychotic drugs and the abnormality of glucose and lipid metabolism have become severe problems in current clinical treatment. These are closely related to diseases such as cardiovascular disease, stroke, diabetes and other diseases, which greatly increase the rate of disability and mortality in patients with mental disorders. Catecholo methyltransferase (COMT) is involved in the regulation of the dopamine function in the prefrontal cortex, which is closely related to the dysfunction of the nerve function. The COMT gene is also a susceptible gene for schizophrenia; methylation, such as methylene four hydrofolate reductase (MTHFR), is involved in the regulation of DNA methylation, including the metabolites of COMT and other compounds. In the process of methylation, the defects of the MTHFR gene will lead to the disorder of several basic biochemical processes in the body. In summary, the COMT and MTHFR genes may be involved in the metabolic abnormalities caused by antipsychotics. This study selects the polymorphic loci of these two genes, COMT (rs4680) and MTHFR (rs1801133), in order to explore the candidate loci and the antipsychotic. The relationship between the metabolic changes caused by the disease drug. Methods: 355 patients were included in the group. All patients received a single atypical antipsychotic treatment. Dynamic observation for 12 weeks, regular measurement of body weight and waist and abdominal circumference, further calculation of body mass index (BMI), extraction of peripheral venous blood at the same time, detection of blood lipids, blood glucose related indexes; Sample DNA was extracted with high salt method, and COMT (rs4680) and MTHFR (rs1801133) genotyping was carried out by mechanism of laser desorption ionization time of flight mass spectrometry (MALDI-TOF-MS). The data of different genotypes were compared before and after treatment with independent sample t test. The index and metabolic changes were compared by independent sample t test. The metabolic index and genotype were compared by variance analysis. Results: 1. among all the patients, there were 155 cases of weight gain, 200 cases in the group without weight gain, and the two groups were statistically significant in age distribution (t=3.254, P0.05), including 88 cases (24.8%), 48 weight gain (31%), 40 (20%) without weight gain, and statistically significant difference between the two groups (x 2=5.634, P0.05). There were 126 patients with metabolic syndrome after drug treatment. In age distribution, the age of metabolic syndrome (MetS) was 41.02 + 11.27 years, and the age of without Met S was 37.55 + 11.38 years. The two groups were statistically significant (P0.05).2. at the baseline level, the weight gain group and the weight loss group were in the index. FPG, T3, and T4 were statistically significant (P 0.05). The weight gain group increased significantly on weight, BMI and waistline (P 0.05), TG, LDL, and CHOL increased significantly (P 0.05), TG, LDL, and CHOL increased significantly (P all 0.05) after a single drug treatment, at the end of a single drug treatment and at the waist circumference (P all 0.05). The weight gain of the olanzapine group was the highest. More, followed by quetiapine group, and finally risperidone group. The three groups of body weight, waist circumference, BMI, LDL and CHOL were statistically significant (P 0.05) the.4.COMT gene genotype and allele frequency between the weight gain group and the body weight group were not statistically significant (P0.05), in men and women. There was no statistical significance (P0.05).COMT gene rs4680 locus and allele frequency in the genotype frequency distribution and allele frequency distribution of Mets or not (P0.05). There were no GG, GA, AA three groups in the distribution of P0.05.5.MTHFR gene (rs1801133) in men and women. There was no statistically significant difference in genotype frequency distribution and allele frequency distribution between the genotype and allele frequencies of.6.MTHFR gene rs1801133 loci and allele frequencies between the weight increase group and the body weight group (P0.05), and there was no statistical significance (P0.05) in both male and female. The genotype and allele frequencies of the rs1801133 loci of the.6.MTHFR gene (P0.05) were statistically significant (P0.05) between the rs1801133 locus and the allele frequencies of the rs1801133 loci of the gene (P0.05). There was no significant difference in the distribution of genotype rs1801133 loci and allele frequencies of MTHFR gene in Mets or not (P0.05). There was no statistical significance in the distribution of male and female (P0.05). Conclusion: 1. atypical antipsychotic drugs can cause significant weight gain, and the weight gain in first and young patients is more likely to occur. In the face of the first and young patients, there was a significant difference in weight change and metabolic changes caused by antipsychotic drugs.2. with different atypical antipsychotics, among which the olanzapine group had the highest weight gain, followed by the quetiapine group and the risperidone group. The three groups were compared to the weight, waist circumference, BMI, LDL, and CHOL. The difference was statistically significant. It showed that the three kinds of drugs not only had significant influence on weight, but also had significant influence on the metabolic index. After the treatment of single antipsychotic drugs, the BMI and waist circumference were also significantly increased in the body weight gain group, and the metabolic index TG, LDL and CHOL were significantly increased, and the difference was statistically significant. In the case of weight gain, there is no significant difference in the distribution of.4.COMT (rs4680) genotypes between the different groups of anti psychotic drugs and different groups, and there is no statistically significant difference in the distribution of the metabolic syndrome and the weight gain in the male and female. COMT (rs4680) and anti semen are not statistically significant. The differences in.5.MTHFR (rs1801133) genotypes of different genotypes in the different genotypes of.5.MTHFR (rs1801133) were statistically significant, indicating that different GG genotypes may be associated with LDL and CHOL metabolism.
【学位授予单位】：天津医科大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R749
本文编号：2170363
[Abstract]:Objective: the weight gain of atypical antipsychotic drugs and the abnormality of glucose and lipid metabolism have become severe problems in current clinical treatment. These are closely related to diseases such as cardiovascular disease, stroke, diabetes and other diseases, which greatly increase the rate of disability and mortality in patients with mental disorders. Catecholo methyltransferase (COMT) is involved in the regulation of the dopamine function in the prefrontal cortex, which is closely related to the dysfunction of the nerve function. The COMT gene is also a susceptible gene for schizophrenia; methylation, such as methylene four hydrofolate reductase (MTHFR), is involved in the regulation of DNA methylation, including the metabolites of COMT and other compounds. In the process of methylation, the defects of the MTHFR gene will lead to the disorder of several basic biochemical processes in the body. In summary, the COMT and MTHFR genes may be involved in the metabolic abnormalities caused by antipsychotics. This study selects the polymorphic loci of these two genes, COMT (rs4680) and MTHFR (rs1801133), in order to explore the candidate loci and the antipsychotic. The relationship between the metabolic changes caused by the disease drug. Methods: 355 patients were included in the group. All patients received a single atypical antipsychotic treatment. Dynamic observation for 12 weeks, regular measurement of body weight and waist and abdominal circumference, further calculation of body mass index (BMI), extraction of peripheral venous blood at the same time, detection of blood lipids, blood glucose related indexes; Sample DNA was extracted with high salt method, and COMT (rs4680) and MTHFR (rs1801133) genotyping was carried out by mechanism of laser desorption ionization time of flight mass spectrometry (MALDI-TOF-MS). The data of different genotypes were compared before and after treatment with independent sample t test. The index and metabolic changes were compared by independent sample t test. The metabolic index and genotype were compared by variance analysis. Results: 1. among all the patients, there were 155 cases of weight gain, 200 cases in the group without weight gain, and the two groups were statistically significant in age distribution (t=3.254, P0.05), including 88 cases (24.8%), 48 weight gain (31%), 40 (20%) without weight gain, and statistically significant difference between the two groups (x 2=5.634, P0.05). There were 126 patients with metabolic syndrome after drug treatment. In age distribution, the age of metabolic syndrome (MetS) was 41.02 + 11.27 years, and the age of without Met S was 37.55 + 11.38 years. The two groups were statistically significant (P0.05).2. at the baseline level, the weight gain group and the weight loss group were in the index. FPG, T3, and T4 were statistically significant (P 0.05). The weight gain group increased significantly on weight, BMI and waistline (P 0.05), TG, LDL, and CHOL increased significantly (P 0.05), TG, LDL, and CHOL increased significantly (P all 0.05) after a single drug treatment, at the end of a single drug treatment and at the waist circumference (P all 0.05). The weight gain of the olanzapine group was the highest. More, followed by quetiapine group, and finally risperidone group. The three groups of body weight, waist circumference, BMI, LDL and CHOL were statistically significant (P 0.05) the.4.COMT gene genotype and allele frequency between the weight gain group and the body weight group were not statistically significant (P0.05), in men and women. There was no statistical significance (P0.05).COMT gene rs4680 locus and allele frequency in the genotype frequency distribution and allele frequency distribution of Mets or not (P0.05). There were no GG, GA, AA three groups in the distribution of P0.05.5.MTHFR gene (rs1801133) in men and women. There was no statistically significant difference in genotype frequency distribution and allele frequency distribution between the genotype and allele frequencies of.6.MTHFR gene rs1801133 loci and allele frequencies between the weight increase group and the body weight group (P0.05), and there was no statistical significance (P0.05) in both male and female. The genotype and allele frequencies of the rs1801133 loci of the.6.MTHFR gene (P0.05) were statistically significant (P0.05) between the rs1801133 locus and the allele frequencies of the rs1801133 loci of the gene (P0.05). There was no significant difference in the distribution of genotype rs1801133 loci and allele frequencies of MTHFR gene in Mets or not (P0.05). There was no statistical significance in the distribution of male and female (P0.05). Conclusion: 1. atypical antipsychotic drugs can cause significant weight gain, and the weight gain in first and young patients is more likely to occur. In the face of the first and young patients, there was a significant difference in weight change and metabolic changes caused by antipsychotic drugs.2. with different atypical antipsychotics, among which the olanzapine group had the highest weight gain, followed by the quetiapine group and the risperidone group. The three groups were compared to the weight, waist circumference, BMI, LDL, and CHOL. The difference was statistically significant. It showed that the three kinds of drugs not only had significant influence on weight, but also had significant influence on the metabolic index. After the treatment of single antipsychotic drugs, the BMI and waist circumference were also significantly increased in the body weight gain group, and the metabolic index TG, LDL and CHOL were significantly increased, and the difference was statistically significant. In the case of weight gain, there is no significant difference in the distribution of.4.COMT (rs4680) genotypes between the different groups of anti psychotic drugs and different groups, and there is no statistically significant difference in the distribution of the metabolic syndrome and the weight gain in the male and female. COMT (rs4680) and anti semen are not statistically significant. The differences in.5.MTHFR (rs1801133) genotypes of different genotypes in the different genotypes of.5.MTHFR (rs1801133) were statistically significant, indicating that different GG genotypes may be associated with LDL and CHOL metabolism.
【学位授予单位】：天津医科大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R749
【参考文献】
相关期刊论文 前3条
1 徐成爱;王雪诗;李申;李洁;;首发精神分裂症血清脂联素及代谢指标与第二代抗精神病药引发肥胖相关性研究[J];中国神经精神疾病杂志;2016年11期
2 吴仁容;赵靖平;邵平;欧建君;常麦会;;抗精神病药物所致体质量增加的遗传易感基因(英文)[J];中南大学学报(医学版);2011年08期
3 中国肥胖问题工作组数据汇总分析协作组 ,周北凡;我国成人适宜体重指数切点的前瞻性研究[J];中华流行病学杂志;2002年06期
，本文编号：2170363
本文链接：https://www.wllwen.com/yixuelunwen/jsb/2170363.html
最近更新
教材专著
