LPHN3 and attention-deficit/hyperactivity disorder: a susceptibility and pharmacogenetic study

被引：50

作者：

Bruxel, E. M. ^{[1
]}

Salatino-Oliveira, A. ^{[1
]}

Akutagava-Martins, G. C. ^{[1
]}

Tovo-Rodrigues, L. ^{[1
]}

Genro, J. P. ^{[1
]}

Zeni, C. P. ^{[2
]}

Polanczyk, G. V. ^{[3
,4
]}

Chazan, R. ^{[2
]}

Schmitz, M. ^{[2
]}

Arcos-Burgos, M. ^{[5
]}

Rohde, L. A. ^{[2
,3
]}

Hutz, M. H. ^{[1
]}

机构：

[1] Univ Fed Rio Grande do Sul, Hosp Clin Porto Alegre, Dept Genet, BR-91501970 Porto Alegre, RS, Brazil

[2] Univ Fed Rio Grande do Sul, Hosp Clin Porto Alegre, Div Child & Adolescent Psychiat, BR-91501970 Porto Alegre, RS, Brazil

[3] Inst Dev Psychiat Children & Adolescents, Porto Alegre, RS, Brazil

[4] Univ Sao Paulo, Sch Med, Dept Psychiat, BR-05508 Sao Paulo, Brazil

[5] Australian Natl Univ, John Curtin Sch Med Res, Dept Gen Biol, Canberra, ACT 2601, Australia

来源：

GENES BRAIN AND BEHAVIOR | 2015年 / 14卷 / 05期

基金：

巴西圣保罗研究基金会;

关键词：

Attention-deficit; hyperactivity disorder; genetic susceptibility; LPHN3; medication response; pharmacogenetics; DEFICIT HYPERACTIVITY DISORDER; CANDIDATE GENE; MOLECULAR-GENETICS; ADHD; METHYLPHENIDATE; ASSOCIATION; LATROPHILIN; SYMPTOMS; CHILDREN; SNP;

D O I：

10.1111/gbb.12224

中图分类号：

B84 [心理学]; C [社会科学总论]; Q98 [人类学];

学科分类号：

03 ; 0303 ; 030303 ; 04 ; 0402 ;

摘要：

Latrophilin 3 (LPHN3) is a brain-specific member of the G-protein coupled receptor family associated to both attention-deficit/hyperactivity disorder (ADHD) genetic susceptibility and methylphenidate (MPH) pharmacogenetics. Interactions of LPHN3 variants with variants harbored in the 11q chromosome improve the prediction of ADHD development and medication response. The aim of this study was to evaluate the role of LPHN3 variants in childhood ADHD susceptibility and treatment response in a naturalistic clinical cohort. The association between LPHN3 and ADHD was evaluated in 523 children and adolescents with ADHD and 132 controls. In the pharmacogenetic study, 172 children with ADHD were investigated. The primary outcome measure was the parent-rated Swanson, Nolan and Pelham Scale - version IV applied at baseline, first and third months of treatment with MPH. The results reported herein suggest the CGC haplotype derived from single nucleotide polymorphisms (SNPs) rs6813183, rs1355368 and rs734644 as an ADHD risk haplotype (P = 0.02, OR = 1.46). Although non-significant after multiple testing correction, its interaction with the 11q chromosome SNP rs965560 slightly increases risk (P = 0.03, OR = 1.55). Homozygous individuals for the CGC haplotype showed faster response to MPH treatment as a significant interaction effect between CGC haplotype and treatment over time was observed (P < 0.001). Homozygous individuals for the GT haplotype derived from SNPs rs6551665 and rs1947275 showed a nominally significant interaction with treatment over time (P = 0.04). Our findings replicate previous findings reporting that LPHN3 confers ADHD susceptibility, and moderates MPH treatment response in children and adolescents with ADHD.

引用

页码：419 / 427

页数：9

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