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      • Record: found
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      No Evidence for Association Between Norepinephrine Transporter-3081 (A/T) Polymorphism and Attention Deficit Hyperactivity Disorder in Iranian Population

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          Abstract

          Background:

          Attention Deficit Hyperactivity Disorder (ADHD) can lead to drastic problems for the patient and its worldwide prevalence is 5%-12%. It also has many comorbidities with other disorders, and the genetic contribution seems the most significant cause.

          Objectives:

          The current study was conducted to investigate the association between norepinephrine transporter-3081 (A/T) polymorphisms and ADHD in Iranian population.

          Patients and Methods:

          Participants were chosen from children and adolescents diagnosed with ADHD referred to Imam Hoseyn Hospital. A child and adolescent psychiatrist confirmed the diagnosis using the Kiddie-Sads-Present and Lifetime Version (K-SADS-PL) semi-structural interview. The control group was from pupils of schools in Tehran (capital city of Iran) who had no history or presence of psychiatric and medical complications. Also, a child and adolescent psychiatrist confirmed their health using the K-SADS-PL semi-structural interview. Genetic examinations were DNA distraction, Polymerase Chain Reaction (PCR), and Restricted Fragment Length Polymorphism (RFLP), which were conducted according to standard protocols. The statistical analysis was performed using chi-square and Fisher's exact test in SPSS version 21.

          Results:

          The percentages of ADHD subtypes for combined, inattentive, and hyperactive/impulsive were 72.2%, 17.2%, and 11.9%, respectively. There was no significant association between norepinephrine transporter polymorphism and ADHD (P = 0.81). Moreover, no significant relationship was found between gender [male (P = 0.92) and female (P = 0.63)] and polymorphism. No significant association was found between subtypes of ADHD [combined (P = 0.46), inattentive (P = 0.41), hyperactive/impulsive (P = 0.32)] and polymorphism SCL6A2. This lack of association can also be seen in gender in every subtype.

          Conclusions:

          The results of the study show no significant association between norepinephrine transporter polymorphism SCL6A2 and ADHD.

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          Most cited references30

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          Molecular genetics of attention-deficit/hyperactivity disorder.

          Stephen V. Faraone, Roy H Perlis, Alysa E Doyle … (2005)
          Results of behavioral genetic and molecular genetic studies have converged to suggest that both genetic and nongenetic factors contribute to the development of attention-deficit/hyperactivity disorder (ADHD). We review this literature, with a particular emphasis on molecular genetic studies. Family, twin, and adoption studies provide compelling evidence that genes play a strong role in mediating susceptibility to ADHD. This fact is most clearly seen in the 20 extant twin studies, which estimate the heritability of ADHD to be .76. Molecular genetic studies suggest that the genetic architecture of ADHD is complex. The few genome-wide scans conducted thus far are not conclusive. In contrast, the many candidate gene studies of ADHD have produced substantial evidence implicating several genes in the etiology of the disorder. For the eight genes for which the same variant has been studied in three or more case-control or family-based studies, seven show statistically significant evidence of association with ADHD on the basis of the pooled odds ratio across studies: DRD4, DRD5, DAT, DBH, 5-HTT, HTR1B, and SNAP-25.
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            Candidate gene studies of ADHD: a meta-analytic review.

            Ian Gizer, Courtney Ficks, Irwin Waldman (2009)
            Quantitative genetic studies (i.e., twin and adoption studies) suggest that genetic influences contribute substantially to the development of attention deficit hyperactivity disorder (ADHD). Over the past 15 years, considerable efforts have been made to identify genes involved in the etiology of this disorder resulting in a large and often conflicting literature of candidate gene associations for ADHD. The first aim of the present study was to conduct a comprehensive meta-analytic review of this literature to determine which candidate genes show consistent evidence of association with childhood ADHD across studies. The second aim was to test for heterogeneity across studies in the effect sizes for each candidate gene as its presence might suggest moderating variables that could explain inconsistent results. Significant associations were identified for several candidate genes including DAT1, DRD4, DRD5, 5HTT, HTR1B, and SNAP25. Further, significant heterogeneity was observed for the associations between ADHD and DAT1, DRD4, DRD5, DBH, ADRA2A, 5HTT, TPH2, MAOA, and SNAP25, suggesting that future studies should explore potential moderators of these associations (e.g., ADHD subtype diagnoses, gender, exposure to environmental risk factors). We conclude with a discussion of these findings in relation to emerging themes relevant to future studies of the genetics of ADHD.
            Article 0 comments Cited 258 times – based on 0 reviews     Review now
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              The analysis of 51 genes in DSM-IV combined type attention deficit hyperactivity disorder: association signals in DRD4, DAT1 and 16 other genes.

              K Brookes, X. Xu, W Chen … (2006)
              Attention deficit hyperactivity disorder (ADHD) is a common neurodevelopmental disorder, starting in early childhood and persisting into adulthood in the majority of cases. Family and twin studies have demonstrated the importance of genetic factors and candidate gene association studies have identified several loci that exert small but significant effects on ADHD. To provide further clarification of reported associations and identify novel associated genes, we examined 1,038 single-nucleotide polymorphisms (SNPs) spanning 51 candidate genes involved in the regulation of neurotransmitter pathways, particularly dopamine, norepinephrine and serotonin pathways, in addition to circadian rhythm genes. Analysis used within family tests of association in a sample of 776 DSM-IV ADHD combined type cases ascertained for the International Multi-centre ADHD Gene project. We found nominal significance with one or more SNPs in 18 genes, including the two most replicated findings in the literature: DRD4 and DAT1. Gene-wide tests, adjusted for the number of SNPs analysed in each gene, identified associations with TPH2, ARRB2, SYP, DAT1, ADRB2, HES1, MAOA and PNMT. Further studies will be needed to confirm or refute the observed associations and their generalisability to other samples.
              Article 0 comments Cited 102 times – based on 0 reviews     Review now
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                Author and article information

                Journal
                Journal ID (nlm-ta): Iran Red Crescent Med J
                Journal ID (iso-abbrev): Iran Red Crescent Med J
                Journal ID (doi): 10.5812/ircmj
                Journal ID (publisher-id): Kowsar
                Title: Iranian Red Crescent Medical Journal
                Publisher: Kowsar
                ISSN (Print): 2074-1804
                ISSN (Electronic): 2074-1812
                Publication date (Electronic): 23 July 2015
                Publication date Collection: July 2015
                Volume: 17
                Issue: 7
                Electronic Location Identifier: e22996
                Affiliations
                [1 ]Behavioral Sciences Research Center, Shahid Beheshti University of Medical Sciences, Tehran, IR Iran
                [2 ]Department of Medical Genetics, Shahid Beheshti University of Medical Sciences, Tehran, IR Iran
                [3 ]Department of Psychiatry, Imam Hosein Hospital, Shahid Beheshti University of Medical Sciences, Tehran, IR Iran
                Author notes
                [* ]Corresponding Authors: Katayoon Razjoyan, Department of Psychiatry, Imam Hosein Hospital, Shahid Beheshti University of Medical Sciences, Tehran, IR Iran. Tel/Fax: +98-2123872572, E-mail: k_razjouyan@ 123456sbmn.ac.ir ; Hossein Darvish, Department of Medical Genetics, Shahid Beheshti University of Medical Sciences, Tehran, IR Iran. Tel/Fax: +98-2123872572, E-mail: darvish_mg@ 123456yahoo.com
                Article
                DOI: 10.5812/ircmj.229961v2
                PMC ID: 4584105
                SO-VID: 25b775c2-d6b0-4825-856a-575dc5233f8d
                Copyright © Copyright © 2015, Iranian Red Crescent Medical Journal.
                License:

                This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International License ( http://creativecommons.org/licenses/by-nc/4.0/) which permits copy and redistribute the material just in noncommercial usages, provided the original work is properly cited.

                History
                Date received : 25 August 2014
                Date revision received : 09 September 2014
                Date accepted : 09 November 2014
                Categories
                Subject: Research Article

                ScienceOpen disciplines: Medicine
                Keywords: scl6a2 protein,humans,attention deficit disorder with hyperactivity,polymorphism, genetic,iran
                Data availability:
                ScienceOpen disciplines: Medicine
                Keywords: scl6a2 protein, humans, attention deficit disorder with hyperactivity, polymorphism, genetic, iran

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