血浆金属硫蛋白3及其基因多态性与儿童自闭症的相关性

Association of plasma metallothionein 3 and its polymorphisms with childhood autism

目的探讨血浆金属硫蛋白3（MT3）及其基因多态性与儿童自闭症的相关性，为自闭症的病因学、分子诊断提供客观依据。方法收集2011年1月至2014年11月武汉地区自闭症特殊学校及湖北省妇幼保健院的自闭症病例132例，并收集同期于武汉大学中南医院就诊和体检的健康儿童316例作为健康对照组。酶联免疫吸附试验检测其中81例白闭症和80例健康儿童的血浆MT3蛋白水平；同时用Sequenom平台的基质辅助激光解吸电离飞行时间质谱对132例自闭症和236例健康儿童M乃基因上的8个单核苷酸多态性（singlenucleotidepolymorphism，SNP）进行基因分型。结果病例组血浆MT3蛋白水平[（740．0±327．4）ng／L]显著低于健康对照组[（1007．1±554．3）ng／L]，差异有统计学意义（P〈0．001）；按性别分层分析发现差异集中于男童（P=0．005）；所有SNP等位基因及基因型分布在2组间差异均无统计学意义（P均〉0．05）。结论MT3蛋白在自闭症儿童血浆中存在表达异常，但此异常可能与其基因多态性无关。

Objective To investigate the association of plasma metallothionein 3 （MT3） and its polymorphisms with childhood autism, in order to provide the objective evidence for autistic etiology and molecular diagnosis. Methods A total of 132 autistic children were recruited from several special autism training schools in Wuhan and the Hubei Maternal and Child Health Hospital between January 2011 and November 2014. Three hundred and sixteen healthy children from the out - patients of Zhongnan Hospital of Wuhan University during the same period were enrolled as healthy controls. Enzyme linked immunosorbent assay was utilized to measure plasma MT3 protein levels in a dataset of 81 cases and 80 controls, while eight single nucleotide polymorphisms （SNP） located in MT3 gene were genotyped in another greater dataset that included 132 cases and 236 controls by the matrix - assisted laser desorption/ionization time of flight mass spectrometry within the Sequenom platform. Results Plasma MT3 protein level was significantly lower in autistic group compared to healthy controls [ （740.0 ± 327.4 ） ng/L vs （ 1 007.1 ± 554.3 ） ng/L,P 〈 0. 001 ], particularly for boys when stratified by gender （ P = 0. 005 ）. No difference existed in any allele or genotype frequencies between the 2 groups （ all P 〉 0.05 ）. Conclusions The selected autistic children harbored abnormal expression profiles of plasma MT3 protein,which may have no connection with its gene polymorphisms.