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Catecholaminergic Gene Variants: Contribution in ADHD and Associated Comorbid Attributes in the Eastern Indian Probands

Authors: Swagata Sinha; Anirban Ray; Keka Sarkar; Kanyakumarika Sarkar; Paramita Ghosh; Kanchan Mukhopadhyay; Nipa Bhaduri;

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.

Keywords

Adult, Male, Adolescent, Genetic Variation, India, Epistasis, Genetic, Comorbidity, Catechol O-Methyltransferase, Polymorphism, Single Nucleotide, Catecholamines, Asian People, Gene Frequency, Aromatic-L-Amino-Acid Decarboxylases, Attention Deficit Disorder with Hyperactivity, Case-Control Studies, Child, Preschool, Dopa Decarboxylase, Humans, Female, Child, Research Article

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citations
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
10
Top 10%
Average
Average
Green
gold