title: Additive effect of three noradrenergic genes (ADRA2a, ADRA2C, DBH) on attention-deficit hyperactivity disorder and learning disabilities in Tourette syndrome subjects.
abstract: Halperin et al. (Halperin JM. Newcorn JH, Koda VH, Pick L, McKay KE, Knott P. Noradrenergic mechanisms in ADHD children with and without reading disabilities: a replication and extension. J Am Acad Child Adolesc Psychiatry 1997: 36: 1688 1696) reported a significant increase in plasma norepinephrine (NE) in attention-deficit hyperactivity disorder (ADHD) children with reading and other cognitive disabilities compared to ADHD children without learning disabilities (LD). We examined the hypothesis that ADHD + LD was associated with NE dysfunction at a molecular genetic level by testing for associations and additive effects between polymorphisms at three noradrenergic genes the adrenergic alpha2A receptor (ADRA2A), adrenergic alpha2C receptor (ADRA2C), and dopamine beta-hydroxylase (DBH) genes. A total of 336 subjects consisting of 274 individuals with Tourette syndrome (TS) and 62 normal controls were genotyped. Regression analysis showed a significant correlation between scores for ADHD, a history of LD, and poor grade-school academic performance that was greatest for the additive effect of all three genes. Combined, these three genes accounted for 3.5% of the variance of the ADHD score (p = 0.0005). There was a significant increase in the number of variant NE genes progressing from subjects without ADHD (A-) or learning disorders (LD-) to A + LD - to A - LD + to A + LD + (p = 0.0017), but no comparable effect for dopamine genes. These data support an association between NE genes and ADHD, especially in ADHD + LD subjects.
authors.affiliation: Department of Medical Genetics, City of Hope Medical Center, Duarte, CA 91010, USA.
authors.forename: D E
authors.initials: DE
authors.lastname: Comings
authors.forename: R
authors.initials: R
authors.lastname: Gade-Andavolu
authors.forename: N
authors.initials: N
authors.lastname: Gonzalez
authors.forename: H
authors.initials: H
authors.lastname: Blake
authors.forename: S
authors.initials: S
authors.lastname: Wu
authors.forename: J P
authors.initials: JP
authors.lastname: MacMurray
mesh_terms: D000293:Adolescent; D000328:Adult; D001289:Attention Deficit Disorder with Hyperactivity / Q000150:complications / Q000235:genetics*; D004299:Dopamine beta-Hydroxylase / Q000235:genetics; D005260:Female; D005796:Genes / Q000235:genetics*; D005838:Genotype; D006801:Humans; D007859:Learning Disabilities / Q000150:complications / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009638:Norepinephrine / Q000378:metabolism; D018341:Receptors, Adrenergic, alpha-2 / Q000235:genetics; D012044:Regression Analysis; D005879:Tourette Syndrome / Q000150:complications / Q000235:genetics*
chemical_list: C547768:ADRA2A protein, human; C547774:ADRA2C protein, human; D018341:Receptors, Adrenergic, alpha-2; D004299:Dopamine beta-Hydroxylase; D009638:Norepinephrine