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LPHN3 and attention-deficit/hyperactivity disorder: a susceptibility and pharmacogenetic study.
Genes Brain Behav 2015; 14(5):419-27GB

Abstract

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.

Authors+Show Affiliations

Genetics Department, Federal University of Rio Grande do Sul, Porto Alegre, RS.Genetics Department, Federal University of Rio Grande do Sul, Porto Alegre, RS.Genetics Department, Federal University of Rio Grande do Sul, Porto Alegre, RS.Genetics Department, Federal University of Rio Grande do Sul, Porto Alegre, RS.Genetics Department, Federal University of Rio Grande do Sul, Porto Alegre, RS.Division of Child and Adolescent Psychiatry, Hospital de Clinicas de Porto Alegre, Federal University of Rio Grande do Sul, Porto Alegre, RS.Institute for Developmental Psychiatry for Children and Adolescents, Porto Alegre, RS. Department of Psychiatry, University of São Paulo Medical School, São Paulo, SP, Brazil.Division of Child and Adolescent Psychiatry, Hospital de Clinicas de Porto Alegre, Federal University of Rio Grande do Sul, Porto Alegre, RS.Division of Child and Adolescent Psychiatry, Hospital de Clinicas de Porto Alegre, Federal University of Rio Grande do Sul, Porto Alegre, RS.Genome Biology Department, The John Curtin School of Medical Research, The Australian National University, Canberra, Australia.Division of Child and Adolescent Psychiatry, Hospital de Clinicas de Porto Alegre, Federal University of Rio Grande do Sul, Porto Alegre, RS. Institute for Developmental Psychiatry for Children and Adolescents, Porto Alegre, RS.Genetics Department, Federal University of Rio Grande do Sul, Porto Alegre, RS.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

25989180

Citation

Bruxel, E M., et al. "LPHN3 and Attention-deficit/hyperactivity Disorder: a Susceptibility and Pharmacogenetic Study." Genes, Brain, and Behavior, vol. 14, no. 5, 2015, pp. 419-27.
Bruxel EM, Salatino-Oliveira A, Akutagava-Martins GC, et al. LPHN3 and attention-deficit/hyperactivity disorder: a susceptibility and pharmacogenetic study. Genes Brain Behav. 2015;14(5):419-27.
Bruxel, E. M., Salatino-Oliveira, A., Akutagava-Martins, G. C., Tovo-Rodrigues, L., Genro, J. P., Zeni, C. P., ... Hutz, M. H. (2015). LPHN3 and attention-deficit/hyperactivity disorder: a susceptibility and pharmacogenetic study. Genes, Brain, and Behavior, 14(5), pp. 419-27. doi:10.1111/gbb.12224.
Bruxel EM, et al. LPHN3 and Attention-deficit/hyperactivity Disorder: a Susceptibility and Pharmacogenetic Study. Genes Brain Behav. 2015;14(5):419-27. PubMed PMID: 25989180.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - LPHN3 and attention-deficit/hyperactivity disorder: a susceptibility and pharmacogenetic study. AU - Bruxel,E M, AU - Salatino-Oliveira,A, AU - Akutagava-Martins,G C, AU - Tovo-Rodrigues,L, AU - Genro,J P, AU - Zeni,C P, AU - Polanczyk,G V, AU - Chazan,R, AU - Schmitz,M, AU - Arcos-Burgos,M, AU - Rohde,L A, AU - Hutz,M H, PY - 2015/03/16/received PY - 2015/04/28/revised PY - 2015/05/13/accepted PY - 2015/5/20/entrez PY - 2015/5/20/pubmed PY - 2016/3/25/medline KW - Attention-deficit/hyperactivity disorder KW - LPHN3 KW - genetic susceptibility KW - medication response KW - pharmacogenetics SP - 419 EP - 27 JF - Genes, brain, and behavior JO - Genes Brain Behav. VL - 14 IS - 5 N2 - 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. SN - 1601-183X UR - https://www.unboundmedicine.com/medline/citation/25989180/LPHN3_and_attention_deficit/hyperactivity_disorder:_a_susceptibility_and_pharmacogenetic_study_ L2 - https://doi.org/10.1111/gbb.12224 DB - PRIME DP - Unbound Medicine ER -