Pharmacogenetics of methylphenidate response and tolerability in attention-deficit/hyperactivity disorder

被引：18

作者：

Pagerols, M. ^{[1
,2
]}

Richarte, V. ^{[2
]}

Sanchez-Mora, C. ^{[1
,2
,3
]}

Garcia-Martinez, I. ^{[1
,2
]}

Corrales, M. ^{[2
]}

Corominas, M. ^{[2
,3
]}

Cormand, B. ^{[4
,5
,6
]}

Casas, M. ^{[2
,3
,7
]}

Ribases, M. ^{[1
,2
,3
]}

Ramos-Quiroga, J. A. ^{[2
,3
,7
]}

机构：

[1] Univ Autonoma Barcelona, Vall dHebron Res Inst VHIR, Psychiat Genet Unit, Passeig Vall dHebron 119-129, Barcelona 08035, Spain

[2] Hosp Univ Vall dHebron, Dept Psychiat, Barcelona, Spain

[3] Biomed Network Res Ctr Mental Hlth CIBERSAM, Barcelona, Spain

[4] Univ Barcelona, Fac Biol, Dept Genet, Barcelona, Spain

[5] CIBERER, Barcelona, Spain

[6] Univ Barcelona IBUB, Inst Biomed, Barcelona, Spain

[7] Univ Autonoma Barcelona, Dept Psychiat & Legal Med, Barcelona, Spain

来源：

PHARMACOGENOMICS JOURNAL | 2017年 / 17卷 / 01期

关键词：

DEFICIT HYPERACTIVITY DISORDER; DOPAMINE TRANSPORTER GENOTYPE; NO SIGNIFICANT ASSOCIATION; IDENTIFIES ASSOCIATION; PRENATAL SMOKING; MATERNAL STRESS; CANDIDATE GENES; DOSE-RESPONSE; ADHD CHILDREN; LPHN3;

D O I：

10.1038/tpj.2015.89

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

Methylphenidate (MPH) is the most frequently used pharmacological treatment in children with attention-deficit/hyperactivity disorder. However, a considerable interindividual variability exists in clinical outcome, which may reflect underlying genetic influences. We analyzed 57 single-nucleotide polymorphisms in 9 dopamine-related candidate genes (TH, DBH, COMT, DAT1 and DRD1-5) as potential predictors of MPH efficacy and tolerability, and we considered prenatal and perinatal risk factors as environmental hazards that may influence treatment effects in a gene-by-environment analysis. Our results provide evidence for the contribution of DRD3 (P = 0.041; odds ratio (OR) = 4.00), DBH (P = 0.032; OR = 2.85), TH (P = 5.5e-03; OR = 4.34) and prenatal smoking (P = 1.7e-03; OR = 5.10) to the clinical efficacy of MPH, with a higher risk for treatment failure in genetically susceptible subjects whose mother smoked during pregnancy. Adverse events after MPH treatment were significantly associated with variation in DBH (P = 6.4e-03; OR = 0.28) and DRD2 (P = 0.047; OR = 3.76). This study suggests that the dopaminergic system together with prenatal smoking exposure may moderate MPH treatment effects.

引用

页码：98 / 104

页数：7

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