Association analysis of apolipoprotein E polymorphisms and weight loss among schizophrenia patients with risperidone treatment

doi:10.12092/j.issn.1009-2501.2019.03.009

Abstract

Abstract:

AIM: To explore the association between apolipoprotein E (APOE) gene polymorphisms and weight change in schizophrenia (SZ) patients induced by antipsychotic treatment. METHODS: 1 516 first-episode SZ patients treated with risperidone, aripiprazole, quetiapine, clozapine, olanzapine and perphenazine for 2 to 7 weeks were followed up. TaqMan genotyping technique was used to detect APOE gene polymorphisms. Cox regression was used to analysis the association between APOE gene variation and risk of weight change induced by drug treatment in SZ patients. RESULTS:The results showed that rs7412 increased the risk of weight loss in patients treated with risperidone, HR (95% CI) was 1.78 (1.01-3.14) with P=0.045. In patients treated with risperidone, the risk of weight loss was higher in carriers of AG/GG genotype of rs405509 than in carriers of AA genotype, HR (95% CI) was 1.75 (1.02-2.98), P value was 0.04. In SZ patients treated with other antipsychotic drugs, the associations between rs769450, rs7412 and rs405509 genotypes (additive model, dominant model and recessive model) with weight change were not found. There was no statistical association; all the P values were more than 0.05. Stratified analysis showed that there was no heterogeneity between rs7412 and rs405509 genotypes (additive model, dominant model and recessive model) and the risk of weight loss in baseline normal weight group and baseline overweight or obesity group (P>0.05). CONCLUSION: rs7412 and rs405509 of APOE increase the risk of weight loss in SZ patients treated by risperidone. Clinician should pay more attention to association between APOE gene rs7412 C>T, rs405509 A>C variations and risperidone-induced weight loss in normal body weight patients.

Key words: schizophrenia, apolipoprotein E, antipsychotic drugs, weight loss

CLC Number:

FAN Yao, XUE Yong, WANG Xin, CHEN Xuefei, ZHANG Xu, YAO Yingshui, SHEN Chong. Association analysis of apolipoprotein E polymorphisms and weight loss among schizophrenia patients with risperidone treatment[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2019, 24(3): 288-295.

References

［1］许梦蓓, 单纯烁, 郑国庆. 精神疾病治疗进展(一):精神分裂症［J］. 医药导报, 2017, 36(10): 1133-1137.
［2］李申. 抗精神病药引发体重和糖脂代谢改变的动态观察及相关基因关联性分析［D］. 天津：天津医科大学，2016.
［3］Alexander ST, Kattula D, Mannam P, et al. Risperidone induced benign intracranial hypertension leading to visual loss［J］. Indian J Psychol Med, 2016, 38(3): 249-251.
［4］Chen CH, Shyue SK, Hsu CP, et al. Atypical antipsychotic drug olanzapine deregulates hepatic lipid metabolism and aortic inflammation and aggravates atherosclerosis［J］. Cell Physiol Biochem, 2018, 50(4): 1216-1229.
［5］刘小蕾, 王志仁, 周晨辉, 等. 奥氮平引起体质量增加的药理学机制研究进展［J］. 国际精神病学杂志, 2015, 42(5): 65-68.
［6］Daray FM, Rodante D, Carosella LG, et al. -759C>T polymorphism of the HTR2C gene is associated with second generation antipsychotic-induced weight gain in female patients with schizophrenia ［J］. Pharmacopsychiatry, 2017, 50(1): 14-18.
［7］Schrder C, Czerwensky F, Leucht S, et al. Fat mass and obesity-related gene variants rs9939609 and rs7185735 are associated with second-generation antipsychotic-induced weight gain ［J］. Pharmacopsychiatry, 2019, 52(1): 16-23.
［8］Hatziri A, Kalogeropoulou C, Xepapadaki E, et al. Site-specific effects of apolipoprotein E expression on diet-induced obesity and white adipose tissue metabolic activation［J］. Biochim Biophys Acta Mol Basis Dis, 2018, 1864(2): 471-480.
［9］陶世武, 杨诚, 陈强, 等. 4种非典型抗精神病药物对精神分裂症患者血糖及血脂代谢的影响［J］. 广西医学, 2009, 31(9): 1238-1241.
［10］王海燕. 抗精神病药物对精神病患者血糖和血脂代谢的影响［J］. 临床医学研究与实践, 2016, 1(16):117.
［11］Poirier J. Apolipoprotein E in animal models of CNS injury and in Alzheimer's disease ［J］. Trends Neurosci, 1994, 17(12): 525-530.
［12］Schürhoff F, Krebs MO, Szake A, et al. Apolipoprotein E in schizophrenia: a French association study and meta-analysis ［J］. Am J Med Genet B Neuropsychiatr Genet, 2003, 119B(1): 18-23.
［13］Gao J, Katagiri H, Ishigaki Y, et al. Involvement of apolipoprotein E in excess fat accumulation and insulin resistance［J］. Diabetes, 2007, 56(1): 24-33.
［14］国际生命科学学会中国办事处中国肥胖问题工作组联合数据汇总分析协作组. 中国成人体质指数分类的推荐意见简介［J］. 中华预防医学杂志, 2001, 35(5): 62-63.
［15］杨闯. 氯氮平体内代谢机制的研究进展［J］. 国外医学.精神病学分册, 2001, 28(1): 35-38.
［16］Tzouvelekis A, Pneumatikos I, Bouros D. Serum biomarkers in acute respiratory distress syndrome an ailing prognosticator ［J］. Respir Res, 2005, 6: 62.
［17］McEvoy JP, Lieberman JA, Perkins DO, et al. Efficacy and tolerability of olanzapine, quetiapine, and risperidone in the treatment of early psychosis: a randomized, double-blind 52-week comparison［J］. Am J Psychiatry, 2007, 164(7): 1050-1060.
［18］伍海姗, 赵丽萍, 赵靖平, 等. 抗精神病药引起体质量增加的药物基因组学研究进展［J］. 中国新药与临床杂志, 2013, 32(7): 507-512.
［19］王雪诗. BDNF基因多态性与抗精神病药导致体质量增加的关联研究［D］. 天津：天津医科大学，2017.
［20］张婷, 张旭, 汪昕, 等. RABEP1基因与精神分裂症患者药物治疗所致体质量变化的关联分析［J］. 临床精神医学杂志, 2017, 27(6): 377-381.
［21］李华芳. 新型抗精神病药:利培酮［J］. 上海精神医学, 1997, 9(1):47-50.
［22］顾牛范, 姚芳传. 利培酮的国内临床应用概况［J］. 中华精神科杂志, 2001, 34(4): 61-63.

[1]	LI Na, HAN Hongcan, WANG Jun. General considerations for bioequivalence studies with pharmacokinetic methods for anti-schizophrenic drugs [J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2021, 26(12): 1419-1425.
[2]	YAN Pan, SHI Jianfei, LI Jing, WANG Shengdong, WANG Shuqi, WANG Chengpeng, SONG Mingfen. Effects of DRD2 and 5-HTR2A gene polymorphisms and their interaction on olanzapine in the treatment of schizophrenia [J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2020, 25(10): 1131-1138.
[3]	WAN Ping, LIU Liang, ZHANG Ping, ZHANG Zhongdong. Influential factors of serum concentration/dosage ratio for schizophrenia patients after oral administration of olanzapine [J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2019, 24(9): 1024-1029.
[4]	CAO Ting, LI Nana, CAI Hualin. Progress in neurosteroids related to the pathogenesis and treatment of schizophrenia [J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2018, 23(6): 709-714.
[5]	CUI Lijun, PAN Xin, ZHU Jielin, LI Jianhua. Effect of paliperidone and olanzapine on patients with first-episode schizophrenia [J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2017, 22(4): 466-470.
[6]	ZHOU Yong, Chen Xuefang, HUANG Hanjin. Efficacy and safety of amisulpride for schizophrenia [J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2017, 22(10): 1152-1157.
[7]	HANG Rong-hua, LI Ye-ping, WU Ming-fei, LI Rui. Relationship on medication compliance, antipsychotic side-effects and social support in schizophrenia outpatients [J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2014, 19(8): 912-915.
[8]	NI Ping, LV Hai-long, GUO Xiao-feng, ZHANG Li-li, XU Lin-yong. Comparison of curative effect and clinical influence factors of risperidone and olanzapine in the treatment of acute phrase of schizophrenia [J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2014, 19(2): 182-185.
[9]	DING Jie-wei¹, WANG Jian-ping². Effects of atorvastatin on ApoA-I and SR-B1 in ApoE-deficient mice [J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2013, 18(11): 1233-1237.
[10]	TANG Ya-mei, ZHANG Xiang-hui, LIU Yong. Concentration change of NE, 5-HT and their metabolites in brain tissue in schizophrenia developmental models rat repeatedly treated with MK-801 [J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2012, 17(7): 721-726.
[11]	HANG Rong-hua, CHENG Wan-liang, WANG Rui-quan, WU Ming-fei. Efficacy and executive function of olanzapine and risperidone in the treatment of elderly patients with schizophrenia [J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2012, 17(7): 812-815.
[12]	LIU Lin-jing, XIU Mei-hong, ZHANG Xiang-yang, CHEN Da-chun. Effect of risperidone on S100B levels and relationship with treatment response in first-episode schizophrenic patients [J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2012, 17(3): 313-317.
[13]	XU Ben-jian, CHEN Ju-feng. Efficacy and safety of paliperidone extended-release tablets as substituting medication in acute patients with schizophrenia [J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2012, 17(2): 215-219.
[14]	WU Xiao-li, WANG Ji-hui, ZHONG Zhi-yong, HAN Zi-li. Therapeutic effects of aripiprazole and olanzapine on the patients with first-episode acute schizophrenia and their influence on plasma prolactin level [J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2011, 16(9): 1016-1020.
[15]	YUAN Guo-feng, YU Yu-li. Control study of paliperidone extended-release tablet and risperidone on negative symptoms of schizophrenia [J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2011, 16(7): 819-822.