Szejko Natalia, Fichna Jakub Piotr, Safranow Krzysztof, Dziuba Tomasz, Żekanowski Cezary, Janik Piotr
Department of Neurology, Medical University of Warsaw, Warsaw, Poland.
Department of Bioethics, Medical University of Warsaw, Warsaw, Poland.
Front Genet. 2020 Mar 4;11:125. doi: 10.3389/fgene.2020.00125. eCollection 2020.
Gilles de la Tourette syndrome (GTS) is a neuropsychiatric disorder of unknown etiology, although a major role of genetic factors has been established. Cannabis-based medicines may alleviate GTS-associated tics and variants of CNR1 gene encoding central cannabinoid receptor (CB1) are believed to be a risk factor for the development of some neurodevelopmental diseases. Our aim was to test the association of selected gene variants with GTS.
The cohort of GTS cases comprised 262 unrelated patients aged 3-53 years (mean age: 18.3 ± 9.1 years; 204 males (77.9%), 126 (48.1%) adults defined as ≥18 years). As a control group we enrolled 279 unrelated, ethnically and gender matched individuals with no diagnosed mental, neurological or general disorder, aged 13-54 years (mean age: 22.5 ± 3.0 years; 200 males, (74.1%). Both study and control groups were selected from Polish population, which is ethnically homogenous subgroup of Caucasian population. Four single nucleotide polymorphisms (SNPs) in were selected: rs2023239, rs2180619, rs806379, and rs1049353 based on minor allele frequency in general population >15%. These variants were genotyped using a real-time quantitative polymerase chain reaction system (TaqMan SNP genotyping assay).
We found significant association of GTS clinical phenotype with rs2023239 variant. Minor allele C and CT+CC genotypes were found significantly more often in GTS patients compared to controls (17.4 vs 11.1%, p=0.003 and 32.8 vs 20.4%, p=0.001, respectively), and the difference remained significant after correction for multiple testing. C allele of rs2023239 polymorphism of the CNR1 gene was associated with the occurrence of tics. There were no statistically significant associations for rs806379, rs1049353 or rs2180619 variants.
Our findings suggest that C allele of rs2023239 polymorphism of the gene is a risk factor of GTS in Polish population. The variant can be potentially associated with abnormal endocannabinoid transmission, which is suspected to be one of the causes of GTS.
尽管遗传因素的主要作用已得到证实，但抽动秽语综合征（GTS）是一种病因不明的神经精神疾病。基于大麻的药物可能会缓解与GTS相关的抽动症状，并且编码中枢大麻素受体（CB1）的CNR1基因变体被认为是某些神经发育疾病发生的危险因素。我们的目的是测试所选基因变体与GTS之间的关联。
GTS病例队列包括262名年龄在3至53岁之间的无亲缘关系患者（平均年龄：18.3±9.1岁；204名男性（77.9%），126名（48.1%）成年人定义为≥18岁）。作为对照组，我们纳入了279名无亲缘关系、种族和性别匹配且未诊断出精神、神经或全身性疾病的个体，年龄在13至54岁之间（平均年龄：22.5±3.0岁；200名男性，（74.1%）。研究组和对照组均选自波兰人群，波兰人群是白种人群中种族同质的亚组。基于一般人群中次要等位基因频率>15%，选择了CNR1基因中的四个单核苷酸多态性（SNP）：rs2023239、rs2180619、rs806379和rs1049353。使用实时定量聚合酶链反应系统（TaqMan SNP基因分型检测）对这些变体进行基因分型。
我们发现GTS临床表型与rs2023239变体之间存在显著关联。与对照组相比，GTS患者中次要等位基因C以及CT+CC基因型的出现频率明显更高（分别为17.4%对11.1%，p=0.003；32.8%对20.4%，p=0.001），并且在进行多重检验校正后差异仍然显著。CNR1基因rs2023239多态性的C等位基因与抽动症状的发生有关。rs806379、rs1049353或rs2180619变体没有统计学上的显著关联。
我们的研究结果表明，CNR1基因rs2023239多态性的C等位基因是波兰人群中GTS的一个危险因素。该变体可能与内源性大麻素传递异常有关，而内源性大麻素传递异常被怀疑是GTS的病因之一。
