Genetic variations of the melatonin pathway in patients with attention-deficit and hyperactivity disorders

被引：46

作者：

Chaste, Pauline ^{[1
,2
]}

Clement, Nathalie ^{[3
]}

Botros, Hany Goubran ^{[1
,2
]}

Guillaume, Jean-Luc ^{[3
]}

Konyukh, Marina ^{[1
,2
]}

Pagan, Cecile ^{[1
,2
]}

Scheid, Isabelle ^{[1
,2
]}

Nygren, Gudrun

Anckarsater, Henrik ^{[4
,6
]}

Rastam, Maria ^{[7
]}

Stahlberg, Ola ^{[4
]}

Gillberg, I. Carina

Melke, Jonas ^{[8
]}

Delorme, Richard ^{[1
,2
,9
]}

Leblond, Claire ^{[1
,2
]}

Toro, Roberto ^{[1
,2
]}

Huguet, Guillaume ^{[1
,2
]}

Fauchereau, Fabien ^{[1
,2
]}

Durand, Christelle ^{[1
]}

Boudarene, Lydia ^{[1
]}

Serrano, Emilie ^{[1
]}

Lemiere, Nathalie

Launay, Jean Marie ^{[11
]}

Leboyer, Marion ^{[12
,13
]}

Jockers, Ralf ^{[3
,5
]}

Gillberg, Christopher ^{[14
]}

Bourgeron, Thomas ^{[1
,2
,10
]}

机构：

[1] Inst Pasteur, Human Genet & Cognit Funct, F-75015 Paris, France

[2] Inst Pasteur, CNRS, URA 2182, F-75015 Paris, France

[3] Univ Paris 05, CNRS, UMR 8104, Inst Cochin, Paris, France

[4] Gothenburg Univ, Dept Child & Adolescent Psychiat, Gothenburg, Sweden

[5] INSERM, U567, Paris, France

[6] Lund Univ, Inst Clin Sci, Malmo, Sweden

[7] Lund Univ, Dept Clin Sci Lund, Lund, Sweden

[8] Gothenburg Univ, Inst Neurosci & Physiol, Dept Pharmacol, Gothenburg, Sweden

[9] Hop Robert Debre, AP HP, Dept Child & Adolescent Psychiat, F-75019 Paris, France

[10] Univ Paris 07, Paris, France

[11] Hop Lariboisiere, AP HP, Paris EA 3621, Dept Biochem,IFR 139, F-75475 Paris, France

[12] Univ Paris 12, Fac Med, INSERM, U955, Creteil, France

[13] FondaMental Fdn, Creteil, France

[14] St George Hosp, Sch Med, London, England

来源：

JOURNAL OF PINEAL RESEARCH | 2011年 / 51卷 / 04期

关键词：

AA-NAT; ADHD; ASMT; genes; melatonin; receptors; AUTISM SPECTRUM DISORDERS; DEFICIT/HYPERACTIVITY DISORDER; SLEEP; RECEPTORS; CHILDREN; ADHD; COGNITION; INSOMNIA; RHYTHM;

D O I：

10.1111/j.1600-079X.2011.00902.x

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Melatonin is a powerful antioxidant and a synchronizer of many physiological processes. Alteration in melatonin signaling has been reported in a broad range of diseases, but little is known about the genetic variability of this pathway in humans. Here, we sequenced all the genes of the melatonin pathway AA-NAT, ASMT, MTNR1A, MTNR1B and GPR50 in 321 individuals from Sweden including 101 patients with attention-deficit/hyperactivity disorder (ADHD) and 220 controls from the general population. We could find several damaging mutations in patients with ADHD, but no significant enrichment compared with the general population. Among these variations, we found a splice site mutation in ASMT (IVS5+2T>C) and one stop mutation in MTNR1A (Y170X) detected exclusively in patients with ADHD for which biochemical analyses indicated that they abolish the activity of ASMT and MTNR1A. These genetic and functional results represent the first comprehensive ascertainment of melatonin signaling deficiency in ADHD.

引用

页码：394 / 399

页数：6

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