WESTPORT, Sep 15 (Reuters Health) - A 120-base pair duplication polymorphism in the dopamine D4 receptor gene (DRD4) shows preferential transmission with attention deficit hyperactivity disorder (ADHD), according to a report in the September issue of Molecular Psychiatry.

DRD4 is highly expressed in the frontal cortex, which subserves various working memory and attentional processes, and at least one other DRD4 polymorphism has been linked to ADHD, the authors explain.

Dr. James McCracken and colleagues at the UCLA School of Medicine in Los Angeles, California examined the linkage in 197 families between ADHD and a newly described DRD4 polymorphism, consisting of a 120-base pair duplication (the 240 allele) in the gene's 5' untranslated region.

Transmission disequilibrium testing revealed a significant association between the 240 allele and ADHD, the report indicates. The strongest linkage was observed between the 240 allele and the inattentive subtype of ADHD.

Presence of the 240 allele conveyed a 40% greater risk of probable or definite ADHD and an 80% greater risk of ADHD, inattentive subtype, the report indicates.

These relative risks are comparable with those associated with the previously identified DRD4.7 gene variant, the researchers note.

The investigators speculate that the duplication polymorphism may increase the ADHD risk by somehow reducing the transcription or expression of the DRD4 receptor.

"The finding of a minor contribution to risk from the 240-bp polymorphism is consistent with the prevailing notion of ADHD as a polygenic disorder of multifactorial etiology, in which multiple risk genes interact to produce disease liability," the authors conclude. "The interaction of the 120-bp polymorphism with other gene variants at the DRD4 locus and with related neurotransmitter genes is unknown, but merits investigation."

"Lastly," they add, "the 120-bp polymorphism could be tested as a predictor of treatment response in ADHD, and perhaps in other disorders."

(From Reuters Health )