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.

中文翻译：

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LHX6，IMMP2L和AADAC 3'UTR的遗传变异与抽动秽语综合征的关联。

背景：Tourette综合征（TS）是一种神经发育障碍，在儿童早期就表现为运动和发声抽动。这项研究的目的是调查TS候选基因3'非翻译区（3'UTR）中的遗传变异，其与microRNA（miRNA）介导的调控或基因表达具有推测的联系。方法：我们采用计算机方法，在18个候选基因的3'UTR中鉴定出32个变异体，这些变异体可能改变了miRNA的结合位点。在由TS病例和对照（n = 290）以及TS家族三重奏（n = 148）组成的样本中，我们进行了传输不平衡测试（TDT）和荟萃分析。结果：我们发现LIM同源盒6（LHX6）基因中的rs3750486（p = 0.021）与线粒体内膜肽酶亚基2（IMMP2L）基因中的rs7795011正相关（p = 0。029），在我们的荟萃分析中使用TS。TDT显示TS患者芳基乙酰胺脱乙酰基酶（AADAC）基因中rs1042201的A等位基因过度传播（p = 0.029）。结论：这项初步研究为LHX6，IMMP2L和AADAC基因的参与以及表观遗传机制（如改变miRNA介导的TS病因中的基因表达调控）提供了进一步的支持。