目的 探讨CNR1基因甲基化水平与孤独症谱系障碍(ASD)间的关联,为ASD的病因学研究提供理论依据。方法 采用病例对照研究方法,选取2017年6月—2018年12月就诊于哈尔滨医科大学儿童发育行为研究中心及康复机构的30名ASD儿童及年龄性别与之相匹配的30名正常儿童作为研究对象,应用Agena MassArray®飞行质谱分析系统检测两组儿童CNR1基因的甲基化水平,并与ASD发病风险及社交反应量表(SRS)得分进行关联分析。结果 ASD儿童CNR1基因启动子区平均甲基化水平(t=2.224)、CpG_3.4(Z＝2.187)、CpG_9.10.11(t=2.308)和CpG_28.29(t=2.943)位点甲基化水平均高于正常对照儿童,差异有统计学意义(P<0.05);其中CNR1基因启动子区平均甲基化水平(OR=1.117,95%CI:1.003~1.245)、CpG_9.10.11(OR=1.072,95%CI:1.006~1.142)和CpG_28.29(OR=1.078,95%CI:1.018~1.141)位点甲基化水平与ASD发病风险呈正相关(P＜0.05);并且CpG_28.29位点甲基化水平与SRS量表社会动机领域评分呈正相关(r=0.421,P＜0.05)。结论 ASD儿童外周血中存在CNR1基因甲基化水平异常,并且可能与ASD发病风险及社交功能具有相关性,其作用机制值得进一步探讨。
Abstract
Objective To explore the relationship between the methylation level of CNR1 and autism spectrum disorder (ASD), in order to provide a theoretical basis for the etiology of ASD. Methods A case-control study was conducted, recruiting 30 children with ASD from the Child Development and Behavior Research Center of Harbin Medical University and a rehabilitation facility, and 30 matched typically developed children from June 2017 to December 2018. The methylation levels of CNR1 in peripheral blood were measured by the Agena MassArray® Mass Spectrometry System. A univariate conditional Logistic regression model was used to analyze the potential association between the methylation level of CNR1 and the risk of ASD with adjustment for age, BMI, body fat percentage and body fat. The correlations between the methylation level of CNR1 and the score of Social Responsiveness Scale (SRS) were evaluated by Pearson/Spearman correlation analysis. Results The methylation levels of the average methylation (t=2.224), CpG_3.4 (Z=2.187), CpG_9.10.11 (t=2.308), and CpG_28.29 (t=2.943) of the CNR1 promoter region in ASD children were significantly higher than controls (P<0.05). The methylation levels of the average methylation (OR=1.117, 95%CI: 1.003 - 1.245), CpG_9.10.11 (OR= 1.072, 95%CI:1.006 - 1.142), and CpG_28.29 (OR=1.078, 95%CI: 1.018 - 1.141) of the CNR1 promoter region were positively correlated with the risk of ASD (P<0.05). The methylation level of CpG_28.29 in ASD children was positively correlated with the scores of social motivation in SRS (r=0.421, P＜0.05). Conclusions The methylation levels of CNR1 in peripheral blood are abnormal in ASD children and might be correlated with the risk of ASD and social function. The underlying mechanism needs to be further explored.
关键词
孤独症谱系障碍 /
CNR1基因 /
甲基化 /
社交障碍
Key words
autism spectrum disorder /
CNR1 gene /
methylation /
social interaction disorder
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参考文献
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基金
国家自然科学基金面上项目(82173535)
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