本文選題：CYP1A2 + 基因多態(tài)性�。� 參考：《鄭州大學(xué)》2014年碩士論文

【摘要】：目的 1.研究河南地區(qū)漢族人群抑郁癥患者CYP1A2基因C734A及G-2964A位點(diǎn)的多態(tài)性分布。 2.研究CYP1A2基因C734A及G-2964A位點(diǎn)多態(tài)性與度洛西汀治療抑郁癥的臨床療效和不良反應(yīng)的關(guān)系。 方法 1.研究對象223例河南地區(qū)漢族抑郁癥患者，均符合《中國精神疾病分類與診斷標(biāo)準(zhǔn)第3版》抑郁發(fā)作的診斷標(biāo)準(zhǔn)，漢密爾頓抑郁量表（17項(xiàng)）≥17分，年齡18~60歲。 2.基因型檢測采用聚合酶鏈反應(yīng)擴(kuò)增和限制性片段長度多態(tài)性技術(shù),分析CYP1A2基因C734A及G-2964A位點(diǎn)的基因多態(tài)性,然后根據(jù)基因型檢測結(jié)果將受試者分為3種代謝型。 3.臨床效應(yīng)評價(jià)用度洛西�。�60mg/d）對223例受試者進(jìn)行為期6周的抗抑郁治療,用漢密爾頓抑郁量表評定度洛西汀的臨床療效，副反應(yīng)量表評定度洛西汀所致不良反應(yīng)。 4.統(tǒng)計(jì)學(xué)分析使用Hardy-Winberg平衡檢驗(yàn)樣本的群體代表性，基因型與臨床療效的關(guān)系采用方差分析，基因型與不良反應(yīng)的關(guān)系采用χ2檢驗(yàn)。 結(jié)果 1河南地區(qū)漢族抑郁癥患者CYP1A2基因C734A及G-2964A位點(diǎn)多態(tài)性共223例受試者中，C734A位點(diǎn)C/C、C/A和A/A基因型頻率分別為13.90％、45.74％和40.36％；G-2964A位點(diǎn)G/G、G/A、A/A基因型頻率分別為54.71％、36.32％、8.97％。 2不同基因型或代謝型之間度洛西汀臨床療效的比較共220例受試者完成為期6周的抗抑郁治療。 2.1CYP1A2/C734A不同基因型間HAMD減分率的比較：治療6周末，HAMD減分率3組之間總體比較差異具有統(tǒng)計(jì)學(xué)意義（p0.01），其中C/C組與C/A組相比差異無統(tǒng)計(jì)學(xué)意義（p0.05），2組分別與A/A組相比均差異有統(tǒng)計(jì)學(xué)意義（均p0.01）。 2.2CYP1A2/G-2964A不同基因型間HAMD減分率的比較：治療6周末,HAMD減分率3組之間總體比較差異有統(tǒng)計(jì)學(xué)意義（p0.01），其中G/A組與A/A組相比差異無統(tǒng)計(jì)學(xué)意義（p0.05），2組分別與G/G組相比均差異有統(tǒng)計(jì)學(xué)意義（均p0.01）。 2.3不同代謝型間HAMD減分率的比較：治療6周末，3組之間HAMD減分率總體比較差異有統(tǒng)計(jì)學(xué)意義（p0.01），兩兩比較均差異有統(tǒng)計(jì)學(xué)意義（均p0.01）。 3不同基因型或代謝型之間度洛西汀所致不良反應(yīng)的比較 223例受試者中，3例受試者在治療早期因嚴(yán)重不良反應(yīng)脫落，均計(jì)入不良反應(yīng)發(fā)生組。 3.1CYP1A2/C734A不同基因型間不良反應(yīng)的比較：3組基因型患者不良反應(yīng)發(fā)生率總體比較差異有統(tǒng)計(jì)學(xué)意義（P0.01），其中C/C組與C/A組相比差異無統(tǒng)計(jì)學(xué)意義（p0.05），2組分別與A/A組相比均差異具有統(tǒng)計(jì)學(xué)意（p0.05、p0.01）。 3.2CYP1A2/G-2964A不同基因型間不良反應(yīng)的比較：3組基因型患者不良反應(yīng)發(fā)生率總體比較差異有統(tǒng)計(jì)學(xué)意義（P0.01），其中G/A組與A/A組相比差異無統(tǒng)計(jì)學(xué)意義（p0.05），2組與G/G組相比均差異有統(tǒng)計(jì)學(xué)意義（均P0.01）。 3.3不同代謝型間不良反應(yīng)的比較：3組基因型患者不良反應(yīng)發(fā)生率總體比較差異有統(tǒng)計(jì)學(xué)意義（P0.05），，兩兩比較差異均具有統(tǒng)計(jì)學(xué)意義（均p0.05）； 結(jié)論 1.河南地區(qū)漢族抑郁癥患者與長沙地區(qū)漢族健康人群之間在CYP1A2/C734A位點(diǎn)的多態(tài)性分布無明顯差異，而兩者在CYP1A2/G-2964A位點(diǎn)的多態(tài)性分布有一定差異。 2. CYP1A2基因C734A及G-2964A位點(diǎn)多態(tài)性可影響度洛西汀治療抑郁癥的臨床療效和不良反應(yīng)。
[Abstract]:objective
1. to study the polymorphisms of CYP1A2 gene C734A and G-2964A loci in patients with depression in Henan Han population.
2. to study the relationship between the polymorphism of C734A and G-2964A locus of CYP1A2 gene and the clinical efficacy and adverse reactions of duloxetine in the treatment of depression.
Method
1. the 223 cases of Han depression in Henan area were all in accordance with the criteria for the classification and diagnosis of Chinese mental diseases and the diagnostic standard third for depression, and the Hamilton Depression Scale (17) was more than 17, and the age was 18~60 years.
2. genotypes were detected by polymerase chain reaction amplification and restriction fragment length polymorphism, and the gene polymorphism of C734A and G-2964A loci of CYP1A2 gene was analyzed. Then the subjects were divided into 3 metabolic types according to the results of genotypic detection.
3. 60mg/d was used for a 6 week antidepressant treatment of 223 subjects. The Hamilton depression scale was used to evaluate the clinical efficacy of duloxetine, and the side reaction scale was used to assess the adverse effects of luoxetine.
4. statistical analysis used the group representativeness of the Hardy-Winberg balance test sample. The relationship between genotypes and clinical efficacy was analyzed by variance analysis. The relationship between genotype and adverse reaction was tested by chi 2 test.
Result
1 among 223 subjects with CYP1A2 gene C734A and G-2964A polymorphism in the Henan Han depression, the frequencies of C734A loci C/C, C/A and A/A genotypes were 13.90%, 45.74% and 40.36%, respectively, and G-2964A loci G/G, G/A, and A/A genotype frequencies were 54.71%, 36.32%, and 8.97%..
2 the clinical efficacy of duloxetine between different genotypes or metabolites was 220. The subjects completed 6 weeks of antidepressant treatment.
The comparison of the reduction rate of HAMD among different genotypes of 2.1CYP1A2/C734A: the total difference between the 3 groups of the HAMD reduction rate in the 6 weekend was statistically significant (P0.01), and there was no statistical difference between the C/C group and the C/A group (P0.05), and the difference between the 2 groups was statistically significant compared with the A/A group (all P0.01).
The comparison of the reduction rate of HAMD among different genotypes of 2.2CYP1A2/G-2964A: the total difference between the 3 groups of the HAMD reduction rate in the 6 weekend was statistically significant (P0.01), and there was no statistical difference between the G/A group and the A/A group (P0.05), and the difference between the 2 groups was statistically significant compared with the G/G group (all P0.01).
2.3 the comparison of the reduction rate of HAMD between different metabolic types: the total difference of HAMD reduction rate among the 3 groups was statistically significant (P0.01), and the difference of 22 was statistically significant (P0.01).
3 Comparison of adverse reactions induced by duloxetine between different genotypes or metabolic types
Of the 223 subjects, 3 of the subjects fell off due to serious adverse reactions at the early stage of treatment, and all of them were included in the group of adverse reactions.
The comparison of the adverse reactions among different genotypes in 3.1CYP1A2/C734A: there was a significant difference in the incidence of adverse reactions between the 3 groups of genotypes (P0.01), and there was no significant difference between the group C/C and the C/A group (P0.05), and the differences in the 2 groups were all compared with the A/A group (P0.05, P0.01).
The comparison of the adverse reactions among different genotypes of 3.2CYP1A2/G-2964A: the incidence of adverse reactions in the 3 groups was statistically significant (P0.01), and there was no significant difference between the group G/A and the A/A group (P0.05), and the difference between the 2 groups was statistically significant compared with the G/G group (P0.01).
3.3 comparison of the adverse reactions among different metabolic types: there was a significant difference in the incidence of adverse reactions between the 3 groups (P0.05), and 22 of the differences were statistically significant (P0.05).
conclusion
1. there is no significant difference in the polymorphism distribution of the CYP1A2/C734A loci between the Han people with depression in Henan and the healthy people of the Han nationality in Changsha, but there are some differences in the polymorphism distribution at the CYP1A2/G-2964A loci.
2. the polymorphism of CYP1A2 gene C734A and G-2964A can affect the clinical efficacy and side effects of duloxetine in the treatment of depression.
【學(xué)位授予單位】：鄭州大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2014
【分類號(hào)】：R96

【參考文獻(xiàn)】

相關(guān)期刊論文 前4條

1 杜波;高成閣;王剛;謝世平;許秀峰;譚慶榮;栗克清;;鹽酸度洛西汀腸溶膠囊治療抑郁癥的療效和安全性[J];中國臨床藥理學(xué)雜志;2009年02期

2 韓興梅,陳小平,吳啟南,蔣長虹,周宏灝;中國人群中CYP1A2基因G-2964A和C734A多態(tài)性分布<英文>[J];Acta Pharmacologica Sinica;2000年11期

3 ;Association of CYP2D6 and CYP1A2 gene polymorphism with tardive dys-kinesia in Chinese schizophrenic patients[J];Acta Pharmacologica Sinica;2006年03期

4 江開達(dá);李凌江;王剛;司天梅;黃繼忠;許秀峰;方貽儒;李惠春;陸崢;梅其一;賈福軍;李濤;趙靖平;吳文源;張明園;;度洛西汀治療抑郁癥及廣泛性焦慮障礙臨床應(yīng)用指導(dǎo)建議[J];中國新藥與臨床雜志;2012年09期

本文編號(hào)：1975467