No evidence of association of two 5HT transporter gene polymorphisms and attention deficit hyperactivity disorder

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Abstract

OBJECTIVES: Three studies to date have found evidence (or a trend for evidence) of linkage and association between the long allele of the 44 base pair repeat insertion/deletion 5-HTT functional polymorphism (5-HTTLPR) and attention deficit hyperactivity disorder (ADHD). In an attempt to replicate these findings, we examined this polymorphism and a variable number tandem repeat in the second intron of 5-HTT for association with ADHD. METHODS: One hundred and fifty children who met diagnostic criteria for ADHD and their parents (where available) were genotyped for these polymorphisms. Analysis was undertaken using the transmission disequilibrium test and haplotype analysis, as well as case-control comparisons using a control group of 121 individuals. RESULTS: No association between either the 5-HTTLPR or the variable number tandem repeat (VNTR) in ADHD was found (extended transmission disequilibrium test; P=0.37 and P=0.62, respectively). Haplotype analysis was also non-significant. Further analysis revealed no evidence of association in the subgroups of those without conduct disorder and in medication non-responders. CONCLUSIONS: Failure to replicate findings from previous studies may be due to a lack of statistical power. However, given recent findings by Kent et al. (2002) of association with another polymorphism in the 5HTT gene, we hypothesise that previous positive findings may have arisen by the LPR and VNTR being in linkage disequilibrium with the true susceptibility polymorphism

Keyword(s)

Conduct Disorder; Linkage Disequilibrium; Parents; Wales; analysis; methods

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