目的 检测北方汉族孤独症谱系障碍(ASD)患儿NPR1基因启动子区的甲基化水平,并探讨其与ASD的相关性。方法 应用焦磷酸测序法检测9对同卵双生ASD样本、30例ASD患儿和30例正常儿童在NPR1基因启动子区2个位点(Chr.1:153652122,Chr.1:153652129)的甲基化水平,并分析其与ASD患儿社交反应量表(SRS)评分之间的相关性。结果 2对同卵双生非共患同胞间在2个检测位点的甲基化水平差异均高于界限值,且ASD病例和对照间比较,差异有统计学意义(P<0.05)。此外,ASD患儿的甲基化水平与SRS量表中“孤独症行为方式”评分呈正相关(P<0.05)。结论 ASD患儿在NPR1基因启动子区的甲基化水平存在异常,且这种异常的甲基化水平与ASD的行为方式相关。
Abstract
Objective To investigate the DNA methylated status of the promoter region of NPR1 gene in autistic children and explore its role in the etiology of autism spectrum disorder (ASD). Methods Totally 9 pairs of ASD-related monozygotic twins, as well as 30 cases of confirmed autism and 30 healthy controls were selected.The DNA methylation level of the promoter region of NPR1 gene (Chr.1:153652122,Chr.1:153652129) was detected by pyrosequencing.The association of the methylation level of ASD cases with the symptoms of ASD which was evaluated by Social Responsiveness Scale (SRS) was analyzed using pearson's correlation analysis. Results A higher difference than standard was found within 2 pairs of ASD-discordant monozygotic twins on the methylation level of the detected loci.Compared with controls,autistic children had higher methylation levels (P<0.05).In addition,the correlation analysis showed a positive correlation between the autistic behavior pattern and the methylation level of the tested loci (P<0.05). Conclusion The methylation level of NPR1 gene in ASD children is abnormal and is positively related to the social behavior of ASD.
关键词
孤独症谱系障碍 /
NPR1基因 /
焦磷酸测序法 /
DNA甲基化 /
社交反应量表
Key words
autism spectrum disorder /
NPR1 gene /
pyrosequencing /
DNA methylation /
Social Responsiveness Scale
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