COMT、MTHFR基因多態(tài)性與抗精神病藥導(dǎo)致代謝異常的關(guān)聯(lián)性研究
發(fā)布時(shí)間：2018-08-07 14:46
【摘要】：目的:非典型抗精神病藥物導(dǎo)致的體重增加及糖,脂代謝異常已經(jīng)成為現(xiàn)今臨床治療中面臨的嚴(yán)峻問(wèn)題,這些都與心血管疾病、中風(fēng)、糖尿病等疾病密切相關(guān),大大增加了精神障礙患者的致殘率和致死率。其中,遺傳因素與之有密切相關(guān),兒茶酚氧位甲基轉(zhuǎn)移酶(COMT)參與調(diào)節(jié)前額葉皮質(zhì)的多巴胺功能,其缺失與神經(jīng)功能失調(diào)密切相關(guān),COMT基因也是精神分裂癥的易感基因;甲基化酶如亞甲基四氫葉酸還原酶(MTHFR)參與調(diào)節(jié)DNA甲基化,包括COMT的代謝產(chǎn)物及其它化合物發(fā)生的甲基化過(guò)程,MTHFR基因的缺陷將導(dǎo)致機(jī)體多個(gè)基礎(chǔ)生化過(guò)程的紊亂。綜上,COMT和MTHFR基因可能參與了抗精神病藥導(dǎo)致代謝異常的過(guò)程,本研究分別選取這兩個(gè)基因上的多態(tài)性位點(diǎn):COMT(rs4680)和MTHFR(rs1801133),以期探究候選位點(diǎn)與抗精神病藥導(dǎo)致的代謝變化之間的關(guān)系。方法:依據(jù)入組排除標(biāo)準(zhǔn)共納入355例患者,所有患者接受單一非典型抗精神病藥物治療。動(dòng)態(tài)觀察12周,定期測(cè)量體重和腰腹圍,進(jìn)一步計(jì)算體質(zhì)指數(shù)(BMI),同時(shí)抽取外周靜脈血,檢測(cè)血脂、血糖相關(guān)指標(biāo);采用高鹽法抽提樣本DNA,以機(jī)制鋪助激光解吸電離飛行時(shí)間質(zhì)譜(MALDI-TOF-MS)進(jìn)行COMT(rs4680)和MTHFR(rs1801133)基因分型。不同基因型治療前后數(shù)據(jù)比較采用獨(dú)立樣本t檢驗(yàn)比較組間指數(shù)及代謝變化情況,采用方差分析比較代謝指標(biāo)與基因型之間的相關(guān)性。結(jié)果:1.在全部患者中,體重增加組共有155例,體重未增加組共有200例,兩組在年齡分布上可見有統(tǒng)計(jì)學(xué)意義(t=3.254,P0.05)。其中首發(fā)88例(24.8%),體重增加有48例(31.0%),體重未增加有40例(20.0%),兩組差異有統(tǒng)計(jì)學(xué)意義(χ2=5.634,P0.05)。經(jīng)藥物治療之后發(fā)展為代謝綜合癥的患者共有126例,在年齡分布上,可見發(fā)生代謝綜合癥(MetS)的年齡是41.02±11.27歲,未發(fā)生Met S的年齡是37.55±11.38歲,兩組差異有統(tǒng)計(jì)學(xué)意義(P0.05)。2.在治療前基線水平,體重增加組與體重未增加組在指標(biāo)FPG、T3和T4差異有統(tǒng)計(jì)學(xué)意義(P均0.05)。相比于體重未增加組,體重增加組在經(jīng)過(guò)單一藥物治療后,在8周末和12周末,在體重、BMI及腰圍上均顯著增加(P均0.05),TG、LDL和CHOL均顯著增加(P均0.05)。3.比較不同抗精神病藥物,發(fā)現(xiàn)奧氮平組體重增加最多,其次是喹硫平組,最后是利培酮組。比較三組的體重,腰圍,BMI,LDL及CHOL的變化,均有統(tǒng)計(jì)學(xué)意義(P均0.05)。4.COMT基因rs4680位點(diǎn)基因型及等位基因頻率在體重增加組與體重未增加組之間的分布差異均無(wú)統(tǒng)計(jì)學(xué)意義(P0.05),在男性和女性中的分布均無(wú)統(tǒng)計(jì)學(xué)意義(P0.05)。COMT基因rs4680位點(diǎn)基因型及等位基因頻率在發(fā)生Mets與否的基因型頻率分布和等位基因頻率分布差異均無(wú)統(tǒng)計(jì)學(xué)意義(P0.05),在男性和女性中的分布均無(wú)統(tǒng)計(jì)學(xué)意義(P0.05)。5.MTHFR基因(rs1801133)的GG、GA、AA三種基因型在△LDL和△CHOL有統(tǒng)計(jì)學(xué)意義(P0.05)。6.MTHFR基因rs1801133位點(diǎn)基因型及等位基因頻率在體重增加組與體重未增加組之間的基因型頻率分布和等位基因頻率分布差異均無(wú)統(tǒng)計(jì)學(xué)意義(P0.05),在男性和女性中的分布均無(wú)統(tǒng)計(jì)學(xué)意義(P0.05)。MTHFR基因rs1801133位點(diǎn)基因型及等位基因頻率在發(fā)生Mets與否的分布差異均無(wú)統(tǒng)計(jì)學(xué)意義(P0.05),男性和女性中的分布均無(wú)統(tǒng)計(jì)學(xué)意義(P0.05)。結(jié)論:1.非典型抗精神病藥物能引起明顯的體重增加,首發(fā)患者及年輕患者更易發(fā)生體重增加。提示面對(duì)首發(fā)及年輕患者時(shí),更應(yīng)慎重選擇抗精神病藥物。2.不同非典型抗精神病藥物導(dǎo)致的體重變化及代謝指標(biāo)的變化有顯著差異,其中奧氮平組體重增加最高,其次是喹硫平組,最后是利培酮組。比較三組在體重,腰圍,BMI,LDL及CHOL的差異均有統(tǒng)計(jì)學(xué)意義。說(shuō)明三種藥物不僅對(duì)體重有明顯影響,對(duì)代謝指標(biāo)也有顯著影響。3.經(jīng)單一抗精神病藥物治療后,體重增加組的除體重外,BMI及腰圍也比體重未增加組顯著增加,代謝指標(biāo)TG、LDL和CHOL均顯著增加,差異有統(tǒng)計(jì)學(xué)意義。說(shuō)明對(duì)體重增加的情況,對(duì)于代謝指標(biāo)的異常也應(yīng)給予高度關(guān)注。4.COMT(rs4680)不同基因型在抗精神病藥物是否導(dǎo)致代謝綜合癥及體重增加不同組間的分布差異無(wú)統(tǒng)計(jì)學(xué)意義,且在男性和女性中的分布均無(wú)統(tǒng)計(jì)學(xué)意義。說(shuō)明COMT(rs4680)與抗精神病藥物導(dǎo)致代謝異常無(wú)相關(guān)性。5.MTHFR(rs1801133)不同基因型在服藥后LDL和CHOL不同變化組間的差異有統(tǒng)計(jì)學(xué)意義,說(shuō)明GG不同基因型可能與LDL和CHOL代謝相關(guān)。
[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.
【學(xué)位授予單位】：天津醫(yī)科大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2017
【分類號(hào)】：R749
本文編號(hào)：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.
【學(xué)位授予單位】：天津醫(yī)科大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2017
【分類號(hào)】：R749
【參考文獻(xiàn)】
相關(guān)期刊論文 前3條
1 徐成愛;王雪詩(shī);李申;李潔;;首發(fā)精神分裂癥血清脂聯(lián)素及代謝指標(biāo)與第二代抗精神病藥引發(fā)肥胖相關(guān)性研究[J];中國(guó)神經(jīng)精神疾病雜志;2016年11期
2 吳仁容;趙靖平;邵平;歐建君;常麥會(huì);;抗精神病藥物所致體質(zhì)量增加的遺傳易感基因(英文)[J];中南大學(xué)學(xué)報(bào)(醫(yī)學(xué)版);2011年08期
3 中國(guó)肥胖問(wèn)題工作組數(shù)據(jù)匯總分析協(xié)作組 ,周北凡;我國(guó)成人適宜體重指數(shù)切點(diǎn)的前瞻性研究[J];中華流行病學(xué)雜志;2002年06期
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