注意缺陷多动障碍认知功能与儿茶酚胺氧位甲基转移酶基因多态性的关联分析
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摘要
目的
探讨ADHD儿童的执行功能特征,COMT基因rs4680和rs6267多态性位点与ADHD及执行功能的关系。
方法
(1)采用STROOP颜色干扰测验、持续性操作测验和威斯康星分类卡片测验对114名符合DSM-Ⅳ诊断标准的ADHD患者和76名正常对照进行执行功能评估,将所得资料进行完全随机设计的方差分析,比较患者组和对照组执行功能。
(2)应用限制性片段长度多态性的SNP分型方法进行COMT基因rs4680和rs6267多态性位点分析,比较患者组和对照组各基因型及等位基因频率分布差异及ADHD组rs4680和rs6267不同基因型与CBCL量表及神经心理测验成绩的相关性。
结果
(1)ADHD组WCST总应答数、完成1分类所需应答数和持续性应答数高于正常对照组(P＜0.05),WCST完成分类数、正确思考时间和不能维持完整分类数低于正常对照组(P＜0.01);CPT错误数和漏报数,STROOP颜色阅读、颜色命名和颜色干扰命名成绩得分均低于正常对照组(P＜0.05),差异均具有统计学意义。
(2)ADHD组与正常对照组COMT基因rs4680和rs6267多态性各基因型及等位基因分布及其在不同性别间的分布,差异均无统计学意义(P＞0.05)。多动冲动型和混合型rs6267多态性各基因型及等位基因频率分布差异均有统计学意义,与混合型相比,多动冲动型G/G型和G等位基因分布均显著增高。
(3)ADHD组rs4680不同基因型WCST概念化水平百分数差异具有统计学意义(P＜0.01),且G/G和A/A之间,G/A和A/A之间,有统计学差异(P＜0.05),即基因型为A/A的ADHD患者的概念化水平百分数较高。ADHD患者rs6267多态性不同基因型CBCL思维问题和违纪问题差异具有统计学意义(P＜0.05),基因型为G/G的患者的思维问题和违纪问题明显多于基因型为G/T的患者。
结论
ADHD儿童存在执行功能缺陷;没有发现COMT基因是ADHD的易感基因;COMT基因rs6267多态性可能与ADHD的某些临床特征或亚型相关,COMT基因rs4680多态性可能与ADHD的某些认知功能有关。
Objectives
To study the cognitive function profiles in children with ADHD. To explore the relationship between rs4680 and rs6267 polymorphism of COMT genes and attention deficit hyperactivity disorder (ADHD).
Methods
114 patients with ADHD and 76 normal controls in Hunan area were involved. We used some neuropsychological tests, including Stroop Word Color Test, Continuous Performance Task (CPT) and Wisconsin Card Sorting Test (WCST) to evaluate the executive function. The significance for the association was estimated by analysis of variance.
The rs4680 and rs6267 polymorphism of COMT genes in these patients and normal controls were examined with polymerase chain reaction and restriction fragment length polymorphism technique. The genotype and allele frequencies of each single nucleotide polymorphism (SNP) were compared between ADHD and normal controls. The relationship was examined between performances of neuropsychological tests and Child Behavior Checklist (CBCL) of ADHD and each SNP.
Results
Compared with control group, the total responses number, responses number on first categories, perseverative responses number of ADHD patients were higher than that of normal control in WCST (P<0.05 ) .But the categories control number, reflections on the correct time, incomplete categories number were lower than that of normal control in WCST (P< 0.01) .Word reading, color naming and the word-color interacting of ADHD patients were poorer than that of normal control in stroop test (P< 0.05) . Error number and omission number of ADHD patients were lower than that of normal control in CPT (P<0.01) .
There was not difference between ADHD normal control in the genotype and allele frequencies of rs4680 and rs6267 polymorphism , no difference of genotype and allele frequencies in sex either (P>0.05 ) . The genotype and allele frequencies rs6267 polymorphism was different between predominantly hyperactive-impulsive type(ADHD-HI) and combined type(ADHD-C) (P<0.01) .The frequency of genotype G/G and allele G in ADHD-HI were significantly higher than that of ADHD-C.
The rs4680 polymorphism was associated with percentage of conceptual level in ADHD patients (P<0.01) , the frequency of genotype A/A was more than others. The rs6267 polymorphism was associated with thinking problem and disciplinary problems of CBCL (P<0.05) ,the frequency of genotype G/G was more than G/T.
Conclusions
The obvious impaired executive functions were found in children with ADHD, but no association was found between the COMT gene and ADHD. However, there might be association between rs6267 polymorphism and some clinical character or subtype of ADHD. The association was found between rs4680 polymorphism and some cognitive function of ADHD too.
探讨ADHD儿童的执行功能特征,COMT基因rs4680和rs6267多态性位点与ADHD及执行功能的关系。
方法
(1)采用STROOP颜色干扰测验、持续性操作测验和威斯康星分类卡片测验对114名符合DSM-Ⅳ诊断标准的ADHD患者和76名正常对照进行执行功能评估,将所得资料进行完全随机设计的方差分析,比较患者组和对照组执行功能。
(2)应用限制性片段长度多态性的SNP分型方法进行COMT基因rs4680和rs6267多态性位点分析,比较患者组和对照组各基因型及等位基因频率分布差异及ADHD组rs4680和rs6267不同基因型与CBCL量表及神经心理测验成绩的相关性。
结果
(1)ADHD组WCST总应答数、完成1分类所需应答数和持续性应答数高于正常对照组(P＜0.05),WCST完成分类数、正确思考时间和不能维持完整分类数低于正常对照组(P＜0.01);CPT错误数和漏报数,STROOP颜色阅读、颜色命名和颜色干扰命名成绩得分均低于正常对照组(P＜0.05),差异均具有统计学意义。
(2)ADHD组与正常对照组COMT基因rs4680和rs6267多态性各基因型及等位基因分布及其在不同性别间的分布,差异均无统计学意义(P＞0.05)。多动冲动型和混合型rs6267多态性各基因型及等位基因频率分布差异均有统计学意义,与混合型相比,多动冲动型G/G型和G等位基因分布均显著增高。
(3)ADHD组rs4680不同基因型WCST概念化水平百分数差异具有统计学意义(P＜0.01),且G/G和A/A之间,G/A和A/A之间,有统计学差异(P＜0.05),即基因型为A/A的ADHD患者的概念化水平百分数较高。ADHD患者rs6267多态性不同基因型CBCL思维问题和违纪问题差异具有统计学意义(P＜0.05),基因型为G/G的患者的思维问题和违纪问题明显多于基因型为G/T的患者。
结论
ADHD儿童存在执行功能缺陷;没有发现COMT基因是ADHD的易感基因;COMT基因rs6267多态性可能与ADHD的某些临床特征或亚型相关,COMT基因rs4680多态性可能与ADHD的某些认知功能有关。
Objectives
To study the cognitive function profiles in children with ADHD. To explore the relationship between rs4680 and rs6267 polymorphism of COMT genes and attention deficit hyperactivity disorder (ADHD).
Methods
114 patients with ADHD and 76 normal controls in Hunan area were involved. We used some neuropsychological tests, including Stroop Word Color Test, Continuous Performance Task (CPT) and Wisconsin Card Sorting Test (WCST) to evaluate the executive function. The significance for the association was estimated by analysis of variance.
The rs4680 and rs6267 polymorphism of COMT genes in these patients and normal controls were examined with polymerase chain reaction and restriction fragment length polymorphism technique. The genotype and allele frequencies of each single nucleotide polymorphism (SNP) were compared between ADHD and normal controls. The relationship was examined between performances of neuropsychological tests and Child Behavior Checklist (CBCL) of ADHD and each SNP.
Results
Compared with control group, the total responses number, responses number on first categories, perseverative responses number of ADHD patients were higher than that of normal control in WCST (P<0.05 ) .But the categories control number, reflections on the correct time, incomplete categories number were lower than that of normal control in WCST (P< 0.01) .Word reading, color naming and the word-color interacting of ADHD patients were poorer than that of normal control in stroop test (P< 0.05) . Error number and omission number of ADHD patients were lower than that of normal control in CPT (P<0.01) .
There was not difference between ADHD normal control in the genotype and allele frequencies of rs4680 and rs6267 polymorphism , no difference of genotype and allele frequencies in sex either (P>0.05 ) . The genotype and allele frequencies rs6267 polymorphism was different between predominantly hyperactive-impulsive type(ADHD-HI) and combined type(ADHD-C) (P<0.01) .The frequency of genotype G/G and allele G in ADHD-HI were significantly higher than that of ADHD-C.
The rs4680 polymorphism was associated with percentage of conceptual level in ADHD patients (P<0.01) , the frequency of genotype A/A was more than others. The rs6267 polymorphism was associated with thinking problem and disciplinary problems of CBCL (P<0.05) ,the frequency of genotype G/G was more than G/T.
Conclusions
The obvious impaired executive functions were found in children with ADHD, but no association was found between the COMT gene and ADHD. However, there might be association between rs6267 polymorphism and some clinical character or subtype of ADHD. The association was found between rs4680 polymorphism and some cognitive function of ADHD too.
引文
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