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利培酮的药物遗传学与儿童及青少年的心血管风险

Pharmacogenetics of Risperidone and Cardiovascular Risk in Children and Adolescents.

作者信息

Dos Santos-Júnior Amilton, Henriques Taciane Barbosa, de Mello Maricilda Palandi, Della Torre Osmar Henrique, Paes Lúcia Arisaka, Ferreira-Neto Adriana Perez, Sewaybricker Letícia Esposito, Fontana Thiago Salum, Celeri Eloisa Helena Rubello Valler, Guerra-Júnior Gil, Dalgalarrondo Paulo

机构信息

Department of Psychiatry, School of Medical Sciences (FCM), State University of Campinas (Unicamp), 13083-887 Campinas, SP, Brazil.

Laboratory of Human Genetics, Center for Molecular Biology and Genetic Engineering (CBMEG), Unicamp, 13083-875 Campinas, SP, Brazil.

出版信息

Int J Endocrinol. 2016;2016:5872423. doi: 10.1155/2016/5872423. Epub 2016 Jan 6.

Abstract

Objective. To identify the frequency of obesity and metabolic complications in child and adolescent users of risperidone. Potential associations with clinical parameters and SNPs of the HTR2C, DRD2, LEP, LEPR, MC4R, and CYP2D6 genes were analyzed. Methods. Samples from 120 risperidone users (8-20 years old) were collected and SNPs were analyzed, alongside assessment of chronological and bone ages, prescribed and weight-adjusted doses, use of other psychotropic drugs, waist circumference, BMI z-scores, blood pressure, HOMA-IR index, fasting levels of serum glucose, insulin, cholesterol, triglycerides, transaminases, and leptin. Results. Thirty-two (26.7%) patients were overweight and 5 (4.2%) obese. Hypertension was recorded in 8 patients (6.7%), metabolic syndrome in 6 (5%), and increased waist circumference in 20 (16.7%). The HOMA-IR was high for 22 patients (18.3%), while total cholesterol and triglycerides were high in 20 (16.7%) and 41 (34.2%) patients, respectively. SNP associations were found for LEP, HTR2C, and CYP2D6 with BMI; CYP2D6 with blood pressure, ALT, and HOMA-IR; HTR2C and LEPR with leptin levels; MC4R and DRD2 with HOMA-IR; HTR2C with WC; and LEP with ALT. Conclusions. Although not higher than in the general pediatric population, a high frequency of patients was overweight/obese, with abnormalities in metabolic parameters and some pharmacogenetic associations.

摘要

目的。确定使用利培酮的儿童和青少年肥胖及代谢并发症的发生率。分析其与临床参数以及5-羟色胺受体2C(HTR2C)、多巴胺受体D2(DRD2)、瘦素(LEP)、瘦素受体(LEPR)、黑皮质素4受体(MC4R)和细胞色素P450 2D6(CYP2D6)基因单核苷酸多态性(SNP)的潜在关联。方法。收集120名使用利培酮的患者(8至20岁)的样本并分析SNP,同时评估其实际年龄和骨龄、规定剂量和体重调整剂量、其他精神药物的使用情况、腰围、体重指数(BMI)z评分、血压、稳态模型评估胰岛素抵抗(HOMA-IR)指数、空腹血清葡萄糖、胰岛素、胆固醇、甘油三酯、转氨酶和瘦素水平。结果。32名(26.7%)患者超重,5名(4.2%)肥胖。8名患者(6.7%)有高血压,6名(5%)有代谢综合征,20名(16.7%)腰围增加。22名患者(18.3%)的HOMA-IR较高,而20名(16.7%)和41名(34.2%)患者的总胆固醇和甘油三酯分别较高。发现LEP、HTR2C和CYP2D6的SNP与BMI有关联;CYP2D6与血压、谷丙转氨酶(ALT)和HOMA-IR有关联;HTR2C和LEPR与瘦素水平有关联;MC4R和DRD2与HOMA-IR有关联;HTR2C与腰围有关联;LEP与ALT有关联。结论。尽管该发生率不高于普通儿科人群,但超重/肥胖患者的比例较高,存在代谢参数异常以及一些药物遗传学关联。

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