GRIN2A、GRIN2B基因多态性与注意缺陷多动障碍的关联研究  

Association of GRIN2A,GRIN2B gene polymorphisms with attention deficit hyperactivity disorder in children

作　　者：丁凯景 丁雨钦[2] 周圆月 刘艳 简凤清 廖文静 童海静 孙玉燕 李艳萍[1] 周国岭 DING Kaijing;DING Yuqin;ZHOU Yuanyue;LIU Yan;JIAN Fengqing;LIAO Wenjing;TONG Haijing;SUN Yuyan;LI Yanping;ZHOU Guoling(Department of Child Psychology,Mental Health Center,Zhejiang University School of Medicine(Hangzhou Seventh People's Hospital),Hangzhou 310013,China)

机构地区：[1]浙江大学医学院附属精神卫生中心(杭州市第七人民医院)儿童心理科,杭州310013 [2]浙江省肿瘤医院乳腺外科

出　　处：《浙江医学》2021年第10期1066-1070,共5页Zhejiang Medical Journal

基　　金：杭州市卫生科技计划项目(2015A32)。

摘　　要：目的探讨N-甲基-D-天冬氨酸受体(NMDAR)亚基NMDA2A基因(GRIN2A)和NMDA2B基因(GRIN2B)单核苷酸多态性与注意缺陷多动障碍(ADHD)的关系。方法选择2016年2月至2018年4月就诊于浙江大学医学院附属精神卫生中心(杭州市第七人民医院)儿童心理科门诊及住院的ADHD患儿(ADHD组)49例及同时期健康体检儿童(健康对照组)50例,抽取外周血样本,提取DNA,根据dbSNP数据库及既往文献选取GRIN2A的rs2229193和GRIN2B的rs2284411作为候选基因位点,设计引物序列,行PCR扩增及结果判读。比较两组GRIN2A基因型频率G/G和G/A,GRIN2B基因型频率C/C和(T/C+T/T)的分布差异。结合ADHD症状评定量表和神经心理测评[SNAP-Ⅳ儿童注意力量表(包含注意缺陷分量表、多动冲动分量表、对立违抗分量表)、中国韦氏儿童智力量表(C-WISC)、Conners父母评症状量表(PSQ)、注意力竞量测验(T.O.V.A.)]得分,比较GRIN2A、GRIN2B不同基因型ADHD患儿的症状。结果两组GRIN2A基因型频率、GRIN2B基因型频率分布比较,差异无统计学意义(P>0.05)。GRIN2A为G/A+A/A基因型的患儿较G/G基因型的患儿有更高的SNAP-IV对立违抗分量表得分以及更高的PSQ品行问题得分,差异均有统计学意义(均P<0.05)。两者SNAP-IV其他分量表得分、C-WISC、PSQ、T.O.V.A.比较,差异均无统计学意义(均P>0.05)。GRIN2B为C/C基因型和T/C+T/T基因型的两种患儿SNAP-IV、C-WISC、PSQ、T.O.V.A.比较,差异均无统计学意义(均P>0.05)。结论GRIN2A中A等位基因携带患儿可能有更多的对立违抗行为和品行问题,提示GRIN2A基因多态性可能与ADHD患儿对立违抗障碍及品行障碍相关。Objective To investigate the relationship of single nucleotide polymorphisms of GRIN2A and GRIN2B gene with attention deficit hyperactivity disorder(ADHD).Methods Forty nine ADHD patients attending Department of Child Psychology of Hangzhou Seventh People's Hospital from February 2016 to April 2018 and 50 healthy children(control group)were enrolled in the study.Peripheral blood samples were collected for DNA extraction.According to the dbSNP database and the published literature,GRIN2A gene rs2229193 and the GRIN2B gene rs2284411 were selected as candidate gene loci.The genotypes of GRIN2A gene rs2229193 and the GRIN2B gene rs2284411 were determined in two groups,and the association of gene polymorphism with ADHD was analyzed.Results There was no significant difference in the distribution of GRIN2A genotype frequency and GRIN2B genotype frequency between the ADHD group and the control group(P>0.05).Compared with the G/G genotype of the GRIN2A gene,patients with G/A+A/A genotype had higher SNAP-IV oppositional defiant subscale score(P<0.05)and higher PSQ character problem item score(P<0.01).There were no significant differences in other SNAP-IV sub-ACGTTGGATGTTGACGAACTTCCGACATGG-scale scores,C-WISC,other PSQ subscale scores,and T.O.V.A.scores between patients with G/G genotype of GRIN2A and those with G/A+A/A genotype(P>0.05).There were no significant differences in SNAP-IV scores,C-WISC scores,PSQ scores,T.O.V.A scores between patients with C/C genotype of GRIN2B and those with T/C+T/T genotype(P>0.05).Conclusion The GRIN2A gene A allele carrier has more opposing defiant behaviors and conduct problems.This result suggests that the GRIN2A gene polymorphismmay be related to ADHD comorbid with opposing defiant disorder and conduct disorder.

关 键 词：注意缺陷多动障碍 基因多态性 对立违抗障碍 品行障碍 

分 类 号：R749.94[医药卫生—神经病学与精神病学]