Transmission disequilibrium of polymorphic variants in the tryptophan hydroxylase-2 gene in attention-deficit/hyperactivity disorder.

Abstract:

:Attention-deficit/hyperactivity disorder (ADHD) is the most common behavioral disorder in childhood with substantial heritability. Pharmacological and molecular genetic studies as well as characterization of animal models have implicated serotonergic dysfunction in the pathophysiology of ADHD. Here, we investigated the effect of polymorphic variants in the gene of the tryptophan hydroxylase-2 (TPH2), the rate-limiting enzyme of serotonin (5-HT) synthesis in the brain, in children and adolescents with ADHD. We analyzed three single nucleotide polymorphisms (SNPs) in and downstream of the transcriptional control region of the TPH2 gene in 103 families with 225 affected children. Allelic association in families with more than one affected child was assessed using the pedigree disequilibrium test. Preferential transmissions were detected for the two SNPs in TPH2's regulatory region (rs4570625, P=0.049; rs11178997, P=0.034), but not for the third SNP in intron 2 (rs4565946, P=0.3517). Haplotype analysis revealed a strong trend of association between the regulatory region SNPs (rs4570625, rs11178997) and ADHD (P=0.064). Our results link potentially functional TPH2 variations to the pathophysiology of ADHD, and further support the relevance of 5-HT in disorders related to altered motor activity and cognitive processes.

journal_name

Mol Psychiatry

journal_title

Molecular psychiatry

authors

Walitza S,Renner TJ,Dempfle A,Konrad K,Wewetzer Ch,Halbach A,Herpertz-Dahlmann B,Remschmidt H,Smidt J,Linder M,Flierl L,Knölker U,Friedel S,Schäfer H,Gross C,Hebebrand J,Warnke A,Lesch KP

doi

10.1038/sj.mp.4001734

subject

Has Abstract

pub_date

2005-12-01 00:00:00

pages

1126-32

issue

12

eissn

1359-4184

issn

1476-5578

pii

4001734

journal_volume

10

pub_type

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