title: Study on DBH genetic polymorphisms and plasma activity in attention deficit hyperactivity disorder patients from Eastern India.
abstract: Dysfunctions in the norepinephric pathway have been speculated in the etiology of attention deficit hyperactivity disorder (ADHD), a common problem for children. Synthesis of norepinephrine from dopamine is catalyzed by the enzyme dopamine beta-hydroxylase and numerous polymorphisms in the DBH gene have been found to exert their direct influence on the enzyme activity independently. In the present study association of ADHD with four genetic polymorphisms, DBH-STR, rs1611115, rs1108580, and rs2519152, was examined in subjects belonging to eastern India. ADHD subjects (n = 111) were recruited following DSM-IV criteria. Peripheral blood samples were collected from nuclear families with ADHD probands. A group of ethnically matched healthy volunteers (n = 130) was also recruited. Genomic DNA was analyzed by PCR amplification followed by restriction digestion and genotyping. Data obtained were subjected to both family-based as well as population-based statistical analyses. Plasma DbetaH activity was measured using a photometric assay and its correlation with the genetic polymorphisms was analyzed using analysis of variance. Case-control analysis revealed no significant differences in allelic frequencies; however, significant paternal over-transmission (P = 0.02) of the rs2519152 'G' allele to ADHD probands was noticed. A haplotype, composed of 12R-C-G-G, also showed biased transmission. Strong correlation was observed between enzyme activity and rs1611115, rs1108580, and rs2519152 (P = 1.51E-6, 0.04, and 0.003, respectively). The present study hints toward the fact that DBH gene polymorphisms have some role in the etiology of ADHD in eastern Indian population and their study could be useful for therapeutic intervention.
authors.affiliation: Manovikas Biomedical Research and Diagnostic Centre, 482, Madudah, Plot I-24, Sec.-J, E.M. Bypass, Kolkata, 700107, India.
authors.forename: Nipa
authors.initials: N
authors.lastname: Bhaduri
authors.forename: Kanyakumarika
authors.initials: K
authors.lastname: Sarkar
authors.forename: Swagata
authors.initials: S
authors.lastname: Sinha
authors.forename: Anindita
authors.initials: A
authors.lastname: Chattopadhyay
authors.forename: Kanchan
authors.initials: K
authors.lastname: Mukhopadhyay
mesh_terms: D001289:Attention Deficit Disorder with Hyperactivity / Q000097:blood / Q000201:enzymology / Q000235:genetics; D004299:Dopamine beta-Hydroxylase / Q000097:blood / Q000235:genetics; D005091:Exons; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D007194:India; D015810:Linkage Disequilibrium; D011110:Polymorphism, Genetic
chemical_list: D004299:Dopamine beta-Hydroxylase