目的 探索珠海地区NRXN1和NLGN1基因多态性与儿童孤独症易感性的关系,为孤独症的防治提供科学依据。方法 采用病例对照的研究方法,选取2011－2016年就诊于珠海市妇幼保健院的123例珠海地区的孤独症患儿和506例健康对照。采用口腔拭子采集口腔上皮细胞以提取DNA,采用Sequenom Mass Array platform分型技术对NRXN1基因上的rs1045881和rs11885824以及NLGN1上的rs9855544进行基因分型。结果 NRXN1基因上的rs1045881和rs11885824以及NLGN1上的rs9855544位点基因型分布在孤独症组和健康对照组比较,差异无统计学意义;但NLGN1基因上的rs9855544与NRXN1基因上的rs11885824存在基因与基因间的交互作用(预测准确率为0.480,交叉验证一致性为10/10,P=0.040)。结论 NRXN1基因上的rs1045881和rs11885824以及NLGN1上的rs9855544位点基因多态性可能与孤独症易感性没有关联,但NLGN1基因上的rs9855544与NRXN1基因上的rs11885824之间的交互作用可能是孤独症易感性的影响因素。
Abstract
Objective To study the association of NRXN1 and NLGN1 with autism spectrum disorder(ASD) in Zhuhai,in order to provide the prevention of ASD. Methods A case-control study was conducted with 123 cases and 506 healthy controls who recruited from Zhuhai Maternal and Child Care Service Centre from 2011 to 2016. Genomic DNA was extracted from oral swabs and the single nucleotide polymorphism(SNP) geno types were determined by using a PCR-RFLP assay. Results There were no significant differences on the distribution of three SNPs (rs1045881 and rs11885824 in NRXN1,rs9855544 in NLGN1) between autism group and healthy controls (P＞0.05) .However,there were significant differences on genotype frequencies between cases and controls for all three polymorphisms. However,interaction between rs11885824 in NRXN1 and rs9855544 in NLGN1 was associated with ASD. The best model was two-locus(rs9855544,rs11885824,Testing accuracy 0.480,CVC10/10,P=0.040). Conclusions Single polymorphisms of rs1045881 and rs11885824 in NRXN1, rs9855544 in NLGN1 are not associated with ASD. However,the interaction between rs11885824 in NRXN1 and rs9855544 in NLGN1 may be involved in the susceptibility to ASD.
关键词
孤独症 /
基因多态性 /
NRXN1 /
NLGN1
Key words
autism spectrum disorder /
genetic polymorphism /
NRXN1 /
NLGN1
{{custom_sec.title}}
{{custom_sec.title}}
{{custom_sec.content}}
参考文献
[1] Lai MC,Lombardo MV,Baron-Cohen S. Autism[J].Lancet,2014,383(9920):896-910.
[2] Huang JP,Cui SS,HanY,et al. Prevalence and early signs of autism spectrum disorder (ASD) among 18-36 month-old children of Tianjin in China[J].Biomed Environ Sci,2014,27(6):453-461.
[3] 杨少萍,陆艳平,彭安娜,等. 武汉市学龄前儿童孤独症筛查及影响因素分析[J].中国妇幼保健,2013,28(10):1613-1616.
[4] Brown EA,Lautz JD,Davis TR,et al. Clustering the autisms using glutamate synapse protein interaction networks from cortical and hippocampal tissue of seven mouse models[J].Molecular Autism,2018,9:48.
[5] He L,Liu X,Song Y,et al.Role of NRXN-NLGN-SHANK pathway gene variations in the pathogenesis of autism spectrum disorders[J].Zhonghua Yi Xue Yi Chuan Xue Za Zhi,2018,35(5):753-756.
[6] Medina MA,Andrade VM,Caracci MO,et al. Wnt/beta-catenin signaling stimulates the expression and synaptic clustering of the autism-associated neuroligin 3 gene[J].Transl Psychiatry,2018,8(1):45.
[7] 刘文文,杜亚松. NRXN1基因在儿童孤独症谱系障碍中的研究进展[J].中国儿童保健杂志,2012,20(4):340-342,384.
[8] Kasem E,Kurihara T,Tabuchi K. Neurexins and neuropsychiatric disorders[J].Neurosci Res,2018,127:53-60.
[9] Kattimani Y,Veerappa AM. Dysregulation of NRXN1 by mutant MIR8485 leads to calcium overload in pre-synapses inducing neurodegeneration in multiple sclerosis[J].Mult Scler Relat Disord,2018,22:153-156.
[10] Todarello G,Feng N,Kolachana BS,et al. Incomplete penetrance of NRXN1 deletions in families with schizophrenia[J].Schizophr Res,2014,155(1-3):1-7.
[11] Grayton HM,Missler M,Collier DA,et al. Altered social behaviours in neurexin 1alpha knockout mice resemble core symptoms in neurodevelopmental disorders[J].PLoS One,2013,8(6):e67114.
[12] Samarelli AV,Riccitelli E,Bizzozero L,et al. Neuroligin 1 induces blood vessel maturation by cooperating with the alpha6 integrin[J].J Biol Chem,2014,289(28):19466-19476.
[13] Zhang Z,Yu H,Jiang S,et al. Evidence for association of cell adhesion molecules pathway and nLGN1 polymorphisms with schizophrenia in Chinese Han population[J].PLoS One,2015,10(12):e0144719.
[14] Nakanishi M,Nomura J,Ji X,et al. Functional significance of rare neuroligin 1 variants found in autism[J].PLoS Genet,2017,13(8):e1006940.
[15]Zeng L,Zhang P,Shi L,et al. Functional impacts of NRXN1 knockdown on neurodevelopment in stem cell models[J].PLoS One,2013,8(3):e59685.
基金
珠海市医疗卫生科技计划项目(20171009E030090)
PDF(495 KB)
