The relationship between the presence of ADHD and certain candidate gene polymorphisms in a Turkish sample

Abstract

Due to the high heritability of attention-deficit hyperactivity disorder (ADHD), parents of children with ADHD appear to represent a good sample group for investigating the genetics of the disorder. The aim of this study was to investigate the association between ADHD and six polymorphisms in five candidate genes [5-HT2A (rs6311), NET1 (rs2242447), COMT (rs4818), NTF3 (rs6332), SNAP-25 (rs3746544) and (rs1051312)]. We included 228 parents of children diagnosed with ADHD and 109 healthy parents as the control group. The polymorphisms were genotyped using polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) assays and analyzed using the chi-square test and the multinomial logit model. SNAP-25 (rs3746544) polymorphism was associated with loading for ADHD, while 5-HT2A (rs6311) and NET1 (rs2242447) polymorphisms were associated with ADHD. On the other hand, there was no significant association between the SNAP-25 (rs1051312), NTF3 (rs6332), or COMT (rs4818) gene polymorphisms and ADHD. In addition, we found that even if variation in the SNAP-25 gene alone does not affect the phenotype, it may nevertheless lead to the emergence of a clinical ADHD picture in the presence of other genetic factors. Our findings suggest that a combination of NET1 (rs2242447) and SNAP-25 (rs3746544) is a risk factor for ADHD. Problems associated with the noradrenergic and serotonergic systems and SNAP-25 may play a role, both alone and in interaction with one another, in the pathophysiological mechanisms of ADHD.

Keywords: 5-HT2; 5-HT2A gene; ADHD; ASRS; COMT; COMT gene; CSS; DSM-IV; Genetics of ADHD; NCBI; NE; NET1 gene; NTF; NTF3 gene; National Center for Biotechnology Information; PCR; RFLP; SCID; SNAP-25; SNAP-25 gene; SNP; Structured Clinical Interview for the DSM-IV; WURS-25; attention-deficit hyperactivity disorder; catechol-O-methyl-transferase; catechol-O-methyl-transferase gene; neurotrophic factor; neurotrophic factor-3 gene; norepinephrine; norepinephrine transporter gene; polymerase chain reaction; restriction fragment length polymorphism; selective serotonin 2A receptor gene; serotonin; single nucleotide polymorphism; synaptosomal-associated protein-25; synaptosomal-associated protein-25 gene; the Adult ADHD Self-Report Scale; the Current Symptom Scale; the Diagnostic and Statistical Manual of Mental Disorders, fourth edition; the Wender-Utah Rating Scale-25.