Nora Angyal1, Zsanett Tarnok2, Edna Grunblatt3, János Réthelyi4,5, Zsofia Nemoda1,5
1 Institute of Medical Chemistry, Molecular Biology and Pathobiochemistry,
Semmelweis University, Budapest, Hungary
2 Vadaskert Child and Adolescent Psychiatric Clinic, Budapest, Hungary
3 Department of Child and Adolescent Psychiatry and Psychotherapy, University Hospital of Psychiatry Zurich, University of Zurich, Zurich, Switzerland
4 Department of Psychiatry and Psychotherapy, Semmelweis University, Budapest, Hungary
5 Molecular Psychiatry Research Group, MTA-SE NAP-B, Hungarian Academy of Sciences, Budapest, Hungary
Introduction: Attention Deficit Hyperactivity Disorder (ADHD) is one of the most common childhood-onset psychiatric disorders, showing high heritability estimates. In this complex inheritance disorder possibly multiple genetic and environmental factors act together during brain development to create a neurobiological susceptibility, similarly to other neurodevelopmental disorders, such as autism spectrum disorders. Altered Wnt-signaling, particularly the lipoprotein receptor-related protein 5 (LRP5) and LRP6 co-receptors, were linked to these disorders. Based on the hypothesis that Wnt-signaling can be involved in the pathogenesis of ADHD, a Swiss workgroup investigated, and found association between LRP5 and LRP6 genes and childhood-onset ADHD.
Aims: Replicate the genetic association of the LRP5 and LRP6 polymorphisms in Hungarian ADHD samples (pediatric and adult) using ADHD diagnosis, as well as symptom severity scores.
Methods: Two single nucleotide polymorphisms (rs4988319 and rs3736228 SNPs) were studied in the LRP5 and two SNPs (rs1012672, rs2302685) in the LRP6 gene. Our case-control study consisted of 191 ADHD children and 267 control subjects. A meta-analysis was performed including Swiss, German and Hungarian pediatric samples. In the dimensional analyses the hyperactivity, impulsivity, and inattention scores of ADHD-Rating Scales collected from 160 ADHD children and 95 adults were analyzed.
Results: In our case-control association study only tendentious association was found between LRP6 rs2302685 and ADHD (p=0.09). Since similar associations could be observed in other European samples, a meta-analysis was conducted, which showed a significant association of the LRP6 rs2302685 with pediatric ADHD (OR=1.21, 95% CI 1.03-1.41; p=0.02). Our dimensional analysis also showed association between LRP6 rs2302685 and ADHD inattention symptom score among children and adults (p=0.04, and 0.03, respectively).
Conclusion: Our findings suggest that a non-synonymous polymorphism (Val1062Ile) of the LRP6 gene is associated with attention problems, which points to the involvement of Wnt-signaling in the pathogenesis of ADHD.
Acknowledgment: The study was supported by KTIA_NAP_13-2014-0011.
Doctoral School of Molecular Medicine
Supervisor: Zsófia Nemoda
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