PhD Scientific Days 2017

Oral Presentations: Neurosciences

Genetic association analysis of norepinephrine transporter polymorphisms and methylphenidate response in ADHD patients

Előadó neve

Angyal, Nóra

Előadó munkahelye

Department of Medical Chemistry, Molecular Biology and Pathobiochemistry, Semmelweis University

Előadó telefonszáma

+36 1 459 15 00 / 60128

Előadó e-mail címe

angyalnora1@gmail.com

Az előadás címe

Genetic association analysis of norepinephrine transporter polymorphisms and methylphenidate response in ADHD patients

Szerző(k) neve és munkahelye

Nora Angyal1, Erzsebet Zsofia Horvath1, Zsanett Tarnok2, Zsofia Nemoda1
1 Institute of Medical Chemistry, Molecular Biology and Pathobiochemistry, Semmelweis University, Budapest, Hungary
2 Vadaskert Child and Adolescent Psychiatric Clinic, Budapest, Hungary

Szekció

Oral Presentations: Neurosciences

Data of the presenter

Doctoral School: Doctoral School of Molecular Medicine
Program: Pathobiochemistry
Supervisor: Zsófia Nemoda
E-mail address: angyalnora1@gmail.com

Text of the abstract

Introduction: Attention Deficit Hyperactivity Disorder (ADHD) is one of the most prevalent childhood-onset psychiatric disorders, showing high heritability. Genetic factors determining drug responsiveness have been intensively studied, because a well-chosen, individually tailored treatment plan would be important to establish in child and adolescent psychiatry. Methylphenidate (MPH) is the most frequently prescribed drug in ADHD pharmacotherapy, but only 65-70% of ADHD patients benefit from MPH treatment. Hitherto mostly the dopamine transporter gene has been studied and only a few studies analyzed the norepinephrine transporter (NET, SLC6A2) gene in MPH-response, although MPH is a potent inhibitor of both dopamine and norepinephrine transporters.
Aims: A genetic association study of the NET polymorphisms was planned using both ADHD diagnosis and symptom severity score. In addition, we aimed to characterize MPH-response in the patient sample.
Methods: Six single nucleotide polymorphisms (rs28386840, rs2242446, rs3785143, rs3785157, rs5569, rs7194256 SNP) were studied across the NET gene in 163 ADHD children. For case-control analysis 400 control subjects were also genotyped. In the dimensional analyses hyperactivity-impulsivity and inattention scores were used. In the MPH-response analyses genotype frequencies of 90 responders and 32 non-responders were compared by chi-square test, and ANOVA was used to assess symptom improvement among 122 ADHD patients.
Results: The intronic rs3785143 showed an association with inattention symptoms (nominal p-value: 0.011). The haplotype analyses supported this association, and indicated the first haploblock’s importance. Nominally significant association was observed between MPH-response and promoter rs28386840: The non-responder group had more AA genotype compared to responders (67% vs 48%), and the T-allele-present group had better improvement on total and hyperactivity-impulsivity symptoms (p=0.041).
Conclusion: Although none of these findings remained significant after correcting for multiple testing, our results are in agreement with previous findings supporting the role of promoter and 5’ region of the NET gene in ADHD.

Kind

Szabad

Előadás fájl jóváhagyás

nem rendelkezett róla

Előadó

1033

Authors (legacy)

Nora Angyal1, Erzsebet Zsofia Horvath1, Zsanett Tarnok2, Zsofia Nemoda1
1 Institute of Medical Chemistry, Molecular Biology and Pathobiochemistry, Semmelweis University, Budapest, Hungary
2 Vadaskert Child and Adolescent Psychiatric Clinic, Budapest, Hungary