title: Catecholaminergic gene variants: contribution in ADHD and associated comorbid attributes in the eastern Indian probands.
abstract: Contribution of genes in attention deficit hyperactivity disorder (ADHD) has been explored in various populations, and several genes were speculated to contribute small but additive effects. We have assessed variants in four genes, DDC (rs3837091 and rs3735273), DRD2 (rs1800496, rs1801028, and rs1799732), DRD4 (rs4646984 and rs4646983), and COMT (rs165599 and rs740603) in Indian ADHD subjects with comorbid attributes. Cases were recruited following the Diagnostic and Statistical Manual for Mental Disorders-IV-TR after obtaining informed written consent. DNA isolated from peripheral blood leukocytes of ADHD probands (N = 170), their parents (N = 310), and ethnically matched controls (n = 180) was used for genotyping followed by population- and family-based analyses by the UNPHASED program. DRD4 sites showed significant difference in allelic frequencies by case-control analysis, while DDC and COMT exhibited bias in familial transmission (P < 0.05). rs3837091 "AGAG," rs3735273 "A," rs1799732 "C," rs740603 "G," rs165599 "G" and single repeat alleles of rs4646984/rs4646983 showed positive correlation with co-morbid characteristics (P < 0.05). Multi dimensionality reduction analysis of case-control data revealed significant interactive effects of all four genes (P < 0.001), while family-based data showed interaction between DDC and DRD2 (P = 0.04). This first study on these gene variants in Indo-Caucasoid ADHD probands and associated co-morbid conditions indicates altered dopaminergic neurotransmission in ADHD.
authors.affiliation: Manovikas Biomedical Research and Diagnostic Centre, 482 Madudah, Plot I-24, Sector-J, E.M. Bypass, Kolkata 700107, India.
authors.forename: Paramita
authors.initials: P
authors.lastname: Ghosh
authors.forename: Kanyakumarika
authors.initials: K
authors.lastname: Sarkar
authors.forename: Nipa
authors.initials: N
authors.lastname: Bhaduri
authors.forename: Anirban
authors.initials: A
authors.lastname: Ray
authors.forename: Keka
authors.initials: K
authors.lastname: Sarkar
authors.forename: Swagata
authors.initials: S
authors.lastname: Sinha
authors.forename: Kanchan
authors.initials: K
authors.lastname: Mukhopadhyay
mesh_terms: D000293:Adolescent; D000328:Adult; D001142:Aromatic-L-Amino-Acid Decarboxylases / Q000235:genetics*; D044466:Asian People / Q000235:genetics; D001289:Attention Deficit Disorder with Hyperactivity / Q000201:enzymology / Q000453:epidemiology / Q000235:genetics*; D016022:Case-Control Studies; D002394:Catechol O-Methyltransferase / Q000235:genetics*; D002395:Catecholamines / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D015897:Comorbidity; D004296:Dopa Decarboxylase / Q000235:genetics; D004843:Epistasis, Genetic; D005260:Female; D005787:Gene Frequency; D014644:Genetic Variation; D006801:Humans; D007194:India / Q000453:epidemiology; D008297:Male; D020641:Polymorphism, Single Nucleotide; D017448:Receptors, Dopamine D2 / Q000235:genetics*; D050638:Receptors, Dopamine D4 / Q000235:genetics*; D044465:White People / Q000235:genetics; D055815:Young Adult
chemical_list: D002395:Catecholamines; C581293:DRD2 protein, human; C493599:DRD4 protein, human; D017448:Receptors, Dopamine D2; D050638:Receptors, Dopamine D4; C588010:COMT protein, human; D002394:Catechol O-Methyltransferase; D004296:Dopa Decarboxylase; D001142:Aromatic-L-Amino-Acid Decarboxylases