Xu, X., Aysimi, E, Anney, R. J. L., Brookes, K-J., Franke, B., Zhou, K., Buschgens, C., Chen, W., Christiansen, H., Eisenberg, J., Gabriëls, I., Manor, I., Marco, R., Müller, U. C., Mulligan, A., Rommelse, N., Thompson, M., Uebel, H., Banaschewski, T., Buitelaar, J. K., Ebstein, R. P., Gill, M., Miranda, A., Mulas, F., Oades, R. D., Roeyers, H., Rothenberger, A., Sergeant, J. A., Sonuga-Barke, E. J. S., Steinhausen, H-C., Taylor, E. A., Faraone, S. V. & Asherson, P.

No association between two polymorphisms of the serotonin transporter gene and combined type attention deficit hyperactivity disorder. American Journal of Medical Genetics Part B, 147, 1306-1309.
DOI 10.1002/ajmg.b.30737. [Request a copy] [View Article]

Introduction: Several studies report associations between the 5-HT transporter gene (SLC6A4: chromosome locus 17q11.2-12) polymorphisms & ADHD. ---- 5 studies found evidence for association between the long-allele of a 44-base pair insertion/deletion polymorphism (5-HTTLPR) & ADHD or closely related phenotypes. -- 2 studies corroborated this -- decribing an under-representation of the short/short genotype -- while a further 6 studies did not find such an association & 7 studies found no association.

For a second polymorphism within the gene, a variable number tandem repeat (VNTR) within intron 2 (STin2-VNTR), one study demonstrated that the 12/12 genotype was significantly less frequent in ADHD cases vs. controls, while a second study found that the 12-allele was preferentially transmitted to offspring affected with ADHD.

Methods: To provide further clarification of the reported associations, we investigated the association of these 2 markers with ADHD in a sample of 1,020 families with 1,166 combined type ADHD cases in the IMAGE project, using the Transmission Disequilibrium Test. Given the large body of work supporting the association of the promoter polymorphism & mood disorders, we further analysed the group of 199 Ss (15%) with ADHD + mood disorder separately.

1 - No association was found between either of the 2 markers of ADHD in our large multisite study nor with depression within the sample of ADHD cases.

2 - specifically - For STin2-VNTR, 3 alleles (9-repeat, 10-repeat & 12-repeat) were detected in our sample with the most common alleles being the 10-repeat & 12-repeat alleles.

Discussion: The common alleles were not significantly associated with ADHD in this sample & no association for the long or short variants of the 5-HTTLPR

see Oades et al. 2008 in Behav. Brain Funct. on the relationships of 5-HT polymorphisms to impulsivity phenotypes.

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