An international multicenter association study of the serotonin transporter gene in persistent ADHD

作者：Landaas E T; Johansson S; Jacobsen K K; Ribases M; Bosch R; Sanchez Mora C; Jacob C P; Boreatti Huemmer A; Kreiker S; Lesch K P; Kiemeney L A; Kooij J J S; Kan C; Buitelaar J K; Faraone S V; Halmoy A; Ramos Quiroga J A; Cormand B; Reif A; Franke B; Mick E; Knappskog P M; Haavik J^*

来源：Genes, Brain and Behavior, 2010, 9(5): 449-458.

DOI：10.1111/j.1601-183X.2010.00567.x

• Adult attention deficit hyperactivity disorder
• comorbidity
• depression
• gender
• 5-HTT
• 5-HTTLPR
• serotonin
• SERT
• SLC6A4

Attention deficit hyperactivity disorder (ADHD) is a common behavioral disorder affecting children and adults. It has been suggested that gene variants related to serotonin neurotransmission are associated with ADHD. We tested the functional promoter polymorphism 5-HTTLPR and seven single nucleotide polymorphisms in SLC6A4 for association with ADHD in 448 adult ADHD patients and 580 controls from Norway. Replication attempts were performed in a sample of 1454 Caucasian adult ADHD patients and 1302 controls from Germany, Spain, the Netherlands and USA, and a meta-analysis was performed also including a previously published adult ADHD study. We found an association between ADHD and rs140700 [odds ratio (OR ) = 0.67; P = 0.01] and the short (S) allele of the 5-HTTLPR (OR = 1.19; P = 0.06) in the Norwegian sample. Analysis of a possible gender effect suggested that the association might be restricted to females (rs140700: OR = 0.45; P = 0.00084). However, the meta-analysis of 1894 cases and 1878 controls could not confirm the association for rs140700 [OR = 0.85, 95% confidence interval (CI) = 0.67-1.09; P = 0.20]. For 5-HTTLPR, five of six samples showed a slight overrepresentation of the S allele in patients, but meta-analysis refuted a strong effect (OR = 1.10, 95% CI = 1.00-1.21; P = 0.06). Neither marker showed any evidence of differential effects for ADHD subtype, gender or symptoms of depression/anxiety. In conclusion, our results do not support a major role for SLC6A4 common variants in persistent ADHD, although a modest effect of the 5-HTTLPR and a role for rare variants cannot be excluded.

• 出版日期2010-7