波兰人群中ADORA1基因rs2228079和ADORA2A基因rs5751876多态性与抽动秽语综合征的关联
Association of ADORA1 rs2228079 and ADORA2A rs5751876 Polymorphisms with Gilles de la Tourette Syndrome in the Polish Population.
作者信息
Janik Piotr, Berdyński Mariusz, Safranow Krzysztof, Żekanowski Cezary
机构信息
Department of Neurology, Medical University of Warsaw, Warsaw, Poland.
Department of Neurodegenerative Disorders, Mossakowski Medical Research Centre, Polish Academy of Sciences, Warsaw, Poland.
出版信息
PLoS One. 2015 Aug 28;10(8):e0136754. doi: 10.1371/journal.pone.0136754. eCollection 2015.
BACKGROUND
Gilles de la Tourette syndrome (GTS) is a neurodevelopmental disorder characterized by motor and vocal tics. Hyperactivity of dopaminergic transmission is considered a prime abnormality in the pathophysiology of tics. There are reciprocal antagonistic interactions between adenosine and dopamine transmission. The aim of the study was to analyze the association of two polymorphisms, rs2228079 in ADORA1 and rs5751876 in ADORA2A, with the risk of GTS and co-morbid disorders.
MATERIAL AND METHODS
A total of 162 Polish GTS patients and 270 healthy persons were enrolled in the study. Two polymorphisms were selected on the basis of knowledge of SNPs frequencies in ADORA1 and ADORA2A. Chi-square test was used for allelic and genotypic association studies. Association of genotypes with age of tic onset was analyzed with Mann-Whitney test. Multivariate logistic regression was used to find independent predictors of GTS risk.
RESULTS
We found that the risk of GTS was associated with rs2228079 and rs5751876 polymorphisms. The GG+GT genotypes of rs2228079 in ADORA1 were underrepresented in GTS patients (p = 0.011), whereas T allele of rs5751876 in ADORA2A was overrepresented (p = 0.017). The GG genotype of rs2228079 was associated with earlier age of tic onset (p = 0.046). We found also that the minor allele G of rs2228079 was more frequent in GTS patients with depression as compared to the patients without depression (p = 0.015). Also the genotype GG was significantly more frequent in patients with obsessive compulsive disorder/behavior (OCD/OCB, p = 0.021) and depression (p = 0.032), as compared to the patients without these co-morbidities. The minor allele T frequency of rs5751876 was lower in GTS patients with co-morbid attention deficit hyperactivity disorder (p = 0.022), and TT+TC genotypes were less frequent in the non-OCD anxiety disorder group (p = 0.045).
CONCLUSION
ADORA1 and ADORA2A variants are associated with the risk of GTS, co-morbid disorders, and may affect the age of tic onset.
背景
抽动秽语综合征（GTS）是一种神经发育障碍，其特征为运动性和发声性抽动。多巴胺能传递亢进被认为是抽动病理生理学中的主要异常。腺苷与多巴胺传递之间存在相互拮抗作用。本研究旨在分析ADORA1基因的rs2228079和ADORA2A基因的rs5751876这两个多态性与GTS及共病的风险之间的关联。
材料与方法
本研究共纳入162例波兰GTS患者和270名健康人。基于ADORA1和ADORA2A中SNP频率的知识选择了两个多态性。采用卡方检验进行等位基因和基因型关联研究。用曼-惠特尼检验分析基因型与抽动发作年龄的关联。采用多因素逻辑回归来寻找GTS风险的独立预测因素。
结果
我们发现GTS风险与rs2228079和rs5751876多态性相关。ADORA1基因rs2228079的GG + GT基因型在GTS患者中比例较低（p = 0.011），而ADORA2A基因rs5751876的T等位基因比例较高（p = 0.017）。rs2228079的GG基因型与较早的抽动发作年龄相关（p = 0.046）。我们还发现，与无抑郁症的GTS患者相比，有抑郁症的GTS患者中rs2228079的次要等位基因G更为常见（p = 0.015）。此外，与无这些共病的患者相比，患有强迫症/强迫行为（OCD/OCB，p = 0.021）和抑郁症（p = 0.032）的患者中GG基因型明显更为常见。共患注意缺陷多动障碍的GTS患者中rs5751876的次要等位基因T频率较低（p = 0.022），非OCD焦虑症组中TT + TC基因型较少见（p = 0.045）。
结论
ADORA1和ADORA2A变体与GTS风险、共病相关，并可能影响抽动发作年龄。
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