Association of Genetic Variation in the 3'UTR of LHX6, IMMP2L, and AADAC With Tourette Syndrome

Luca Pagliaroli; Andrea Vereczkei; Shanmukha Sampath Padmanabhuni; Zsanett Tarnok; Luca Farkas; Peter Nagy; Renata Rizzo; Tomasz Wolanczyk; Urszula Szymanska; Mira Kapisyzi; Entela Basha; Anastasia Koumoula; Christos Androutsos; Vaia Tsironi; Iordanis Karagiannidis; Peristera Paschou; Csaba Barta

doi:10.3389/fneur.2020.00803

Association of Genetic Variation in the 3'UTR of LHX6, IMMP2L, and AADAC With Tourette Syndrome

Front Neurol. 2020 Aug 14:11:803. doi: 10.3389/fneur.2020.00803. eCollection 2020.

Authors

Luca Pagliaroli¹, Andrea Vereczkei¹, Shanmukha Sampath Padmanabhuni², Zsanett Tarnok³, Luca Farkas³, Peter Nagy³, Renata Rizzo⁴, Tomasz Wolanczyk⁵, Urszula Szymanska⁵, Mira Kapisyzi⁶, Entela Basha⁶, Anastasia Koumoula⁷, Christos Androutsos⁷, Vaia Tsironi⁷, Iordanis Karagiannidis², Peristera Paschou², Csaba Barta¹

Affiliations

¹ Institute of Medical Chemistry, Molecular Biology and Pathobiochemistry, Semmelweis University, Budapest, Hungary.
² Department of Molecular Biology and Genetics, Democritus University of Thrace, Alexandroupoli, Greece.
³ Vadaskert Clinic for Child and Adolescent Psychiatry, Budapest, Hungary.
⁴ Materno Infantile and Radiological Science Department, University of Catania, Catania, Italy.
⁵ Department of Child Psychiatry, Medical University of Warsaw, Warsaw, Poland.
⁶ University Hospital Center "Mother Theresa," Tirana, Albania.
⁷ Department of Child and Adolescent Psychiatry, Sismanoglio General Hospital of Attica, Athens, Greece.

Abstract

Background: Tourette Syndrome (TS) is a neurodevelopmental disorder that presents with motor and vocal tics early in childhood. The aim of this study was to investigate genetic variants in the 3' untranslated region (3'UTR) of TS candidate genes with a putative link to microRNA (miRNA) mediated regulation or gene expression. Methods: We used an in silico approach to identify 32 variants in the 3'UTR of 18 candidate genes putatively changing the binding site for miRNAs. In a sample composed of TS cases and controls (n = 290), as well as TS family trios (n = 148), we performed transmission disequilibrium test (TDT) and meta-analysis. Results: We found positive association of rs3750486 in the LIM homeobox 6 (LHX6) gene (p = 0.021) and rs7795011 in the inner mitochondrial membrane peptidase subunit 2 (IMMP2L) gene (p = 0.029) with TS in our meta-analysis. The TDT showed an over-transmission of the A allele of rs1042201 in the arylacetamide deacetylase (AADAC) gene in TS patients (p = 0.029). Conclusion: This preliminary study provides further support for the involvement of LHX6, IMMP2L, and AADAC genes, as well as epigenetic mechanisms, such as altered miRNA mediated gene expression regulation in the etiology of TS.

Keywords: 3'UTR; SNP; Tourette Syndrome; genetic variation; microRNA.