注意缺陷多动障碍与多巴胺β羟化酶基因的关联分析

Association analysis between DPH polymorphisms and attention deficit hyperactivity disorder

【目的】分析DβH基因与注意缺陷多动障碍(attentiondeficithyperactivitydisordor,ADHD)的关联;探讨ADHD的血浆DβH活性与各基因型的关系。【方法】采用Amp-FLP技术,检测54名ADHD患者及其父母(n=82)和正常对照者(n=30)DβH基因(GT)n多态性的基因型和等位基因频率,运用病例对照研究和核心家系的关联分析(HRR和TDT)分别进行研究,并测定血浆DβH活性。【结果】ADHD组与对照组DβH活性及各基因型的DβH活性差异均无显著性(P>0.05);共发现4种等位基因和8种基因型,A3频率较高。(GT)n多态性各基因型频率和等位基因频率在ADHD组与对照组以及核心家系中的分布差异均无显著性(P均>0.05)。单纯ADHD组A2频率明显高于共病组(P<0.05)。A2/A3型在CBCL的社交、注意、攻击及行为总分得分上均明显高于A3/A3型(P<0.05)。【结论】DβH基因(GT)n多态性与ADHD之间可能不存在关联,某些基因型可能与临床表现有关。

[Objectives] To analysis the association between polymorphisms in human dopamine β-hydroxylase gene and attention deficit hyperactivity disorder（ADHD）, to explore the relationship between DβH activity in plasma and genotypes of DβH gene, and to find the disease-perdisposing genes of ADHD. [Methods] Genotypes and allele frequencies of polymorphic （GT）n repeat at DβH gene in ADHD probands, their parents, and normal controls were examined by Amp-FLP techniques. Both case-control association study and family-based association study （HRR and TDT analysis） were used. Plasma DβH activity was photometrically assayed. [Results] No differences in genotypes and allele frequencies of polymorphic （GT）n repeat at DβH gene were observed between ADHD group and control group （P〈0.05）, and in nuclear families （P〈0.05）. The frequency of A2 allele in “purled” ADHD group was significantly higher than that in cormobid group （P〈0.05）. The scores of social problems, attention problems, aggressive behavior and total behavior scores of CBCL in A2/A3 genotype in ADHD probands were significantly higher than that in A3/A3 genotype in ADHD probands （P〈0.05）. No difference was observed in the level of DβH activity in the plasma between ADHD group and control group （P〉0.05）. Conclusions DβH gene was probably not associated with ADHD in this study. The frequency of A2 allele was probably associated with “purled” ADHD. The polymorphic （GT）n repeat at DβH （P〉0.05）. [Conlusions] DβH gene was probably not associated with ADHD in this study. The frequency of A4 allele of DβH gene in the subjects was very low. The frequency of A2 allele was probably associated with “puried” ADHD. The polymorphic（GT）, repeat at DβH gene was somewhat associatedwith certain clinical manifestations in ADHD;The level of plasma DβH activity in ADHD was not probably associated with different genotypes frequencies of polymorphic（GT）n repeat at DβH gene in this study.