GRIN2A、GRIN2B基因多态性与哌甲酯治疗注意缺陷多动障碍疗效的关系研究  

Association of GRIN2A,GRIN2B gene polymorphisms and the efficacy of methylphenidate in treatment of attention deficit hyperactivity disorder

作　　者：丁凯景 丁雨钦[2] 刘艳 简凤清 孙宁 王少华 周国岭 DING Kaijing;DING Yuqin;LIU Yan;JIAN Fengqing;SUN Ning;WANG Shaohua;ZHOU Guoling(Department of Child Psychology,the Affiliated Mental Health Center&Hangzhou Seventh People's Hospital,Zhejiang University School of Medicine,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,310013 [2]浙江省肿瘤医院乳腺外科

出　　处：《浙江医学》2022年第19期2064-2069,共6页Zhejiang Medical Journal

基　　金：杭州市卫生科技计划项目(A20210567);杭州市第七人民医院高峰学科/杭州市医学重点学科建设项目。

摘　　要：目的探讨GRIN2A基因和GRIN2B基因单核苷酸多态性与哌甲酯治疗注意缺陷多动障碍(ADHD)疗效的关系。方法选择2016年2月至2019年2月杭州市第七人民医院儿童心理科门诊及住院的6~15岁ADHD患儿80例,治疗前抽取外周血3 ml,用试剂盒提取DNA后-80℃冷冻备用。其中74例患儿完成8周的哌甲酯治疗随访,并于治疗前及治疗8周后进行SNAP-IV、中国韦氏儿童智力测试(C-WISC)、Conners父母评症状量表(PSQ)、注意力竞量测验(T.O.V.A.)和神经心理测评。以GRIN2A基因rs2229193和GRIN2B基因rs2284411作为候选基因位点,采用PCR扩增并结果判读。结果GRIN2A基因G/A+A/A基因型患儿的SNAP-IV对立违抗分量表得分、PSQ品行问题项目得分均较G/G基因型高(均P<0.01)。GRIN2B基因T/C+T/T基因型患儿的SNAP-IV注意缺陷分量表得分较C/C基因型更高(P<0.05)。治疗有效和治疗无效患儿间GRIN2A基因G/A+A/A基因型频率与G/G基因型频率、GRIN2B基因T/C+T/T基因型频率与C/C基因型频率比较差异均无统计学意义(均P>0.05);对立违抗改善与未改善患儿的GRIN2A基因G/A+A/A基因型频率与G/G基因型频率比较差异有统计学意义(P<0.05),而GRIN2B基因T/C+T/T基因型频率和C/C基因型频率比较差异无统计学意义(P>0.05)。结论GRIN2A基因中A等位基因携带组在接受哌甲酯治疗后,对立违抗行为显著减少,提示GRIN2A基因多态性可能与哌甲酯改善ADHD患儿对立违抗行为的疗效相关。Objective To investigate the relationship of the single nucleotide polymorphisms of GRIN2A and GRIN2B gene with the efficiency of methylphenidate(MPH)in treatment of attention deficit hyperactivity disorder(ADHD).Methods Eighty ADHD children aged 6-15 years who attended the Affiliated Mental Health Center&Hangzhou Seventh People's Hospital from February 2016 to February 2019 were enrolled in this study.Seventy-four patients received MPH treatment and followed up for 8 week.The SNAP-IV,PSQ,C-WISC,T.O.V.A.and other scales were used for neuropsychological assessments before and after treatment.The polymorphisms of the GRIN2A gene rs2229193 and the GRIN2B gene rs2284411 were detected with PCR.The relationship of GRIN2A and GRIN2B gene polymorphisms with the efficacy of MPH was analyzed.Results The scores of SNAP-IV oppositional defiant subscale and PSQ conduct question items in patients with G/A+A/A genotype of GRIN2A gene were higher than those in G/G genotype(all P<0.01).The SNAP-IV attention deficit subscale scores in patients with GRIN2B gene T/C+T/T genotype were higher than those in C/C genotype(P<0.05).There were no significant differences in the frequencies of G/A+A/A genotype and G/G genotype of GRIN2A gene,and the frequencies of T/C+T/T genotype and C/C genotype of GRIN2B gene between patients with effective and ineffective treatment(all P>0.05).There was a significant difference between G/A+A/A genotype and G/G genotype of GRIN2A gene in patients with and without improvement in oppositional defiance(P<0.05),but there was no significant difference between T/C+T/T genotype and C/C genotype frequency of GRIN2B gene(P>0.05).Conclusion The GRIN2A gene A allele carriers show a significant reduction in oppositional defiant behavior after receiving MPH treatment,which suggests that GRIN2A gene polymorphism may be related to the efficacy of MPH in treatment of ADHD patients.

关 键 词：注意缺陷多动障碍 基因多态性 哌甲酯 对立违抗障碍 药物治疗 

分 类 号：R749.94[医药卫生—神经病学与精神病学]