多巴胺D_4受体基因和5-羟色胺转运体基因与注意缺陷多动障碍及其相关症状的关联分析

Association analysis of dopamine D_4 receptor gene and serotonin transporter promoter gene polymorphisms with attention deficit hyperactivity disorder and related symptomatology

目的探讨多巴胺D4受体(DRD4)基因和5-羟色胺转运体(5HTT)基因与注意缺陷多动障碍(ADHD)及其相关症状的关系。方法利用Achenbach父母用儿童行为调查表评定139例ADHD患儿(患者组)的临床症状;采用聚合酶链反应、聚丙烯酰胺凝胶电泳结合银染技术,检测患者组和115名正常儿童(对照组)的基因型和等位基因频率。结果(1)患者组与对照组间DRD4和5HTT基因的基因型及等位基因频率分布的差异无统计学意义(P>0.05)。(2)5HTT基因的S/S基因型个体的社会退缩[(4.4±3.0)分]、躯体主诉[(3.6±2.7)分]得分高于S/L+L/L基因型个体[(3.3±2.6)分和(2.6±2.6)分],差异有统计学意义(P<0.05)。(3)在非携带DRD4基因3等位基因个体中,S/L+L/L基因型的注意问题[(10.4±3.1)分]和社交问题[(7.2±3.7)分]得分高于S/S基因型个体[分别为(8.7±3.1)分和(5.3±2.3)分],差异有统计学意义(P<0.05)。结论DRD4基因和5HTT基因与ADHD可能无关联;但5HTT基因与ADHD的某些内化性症状可能存在关联;对ADHD的某些症状(注意问题和社交问题),DRD4基因与5HTT可能存在相互协同作用。

Objective To investigate the relationship between 48 bp variant number tandem repeat（VNTR） polymorphism in the third exon of dopamine D4 receptor （DRD4） gene and serotonin transporter promoter polymorphism （5-HTTLPR） and attention deficit hyperactivity disorder （ADHD）. Methods 139 children with ADHD and 115 normal controls in Hunan area were involved. The patients＇ clinical symptoms were assessed with the Child Behavior Checklist （CBCL）. The genotype and allele frequencies were obtained after the regions of DRD4 and 5-HTTLPR genes containing the polymorhpism site amplified by the polymerase chain reaction and denatured with the polyacrylamide gel electrophoresis and silver staining. Results There were no significant differences in the frequencies of the genotypes and alleles of DRD4 and 5-HTTLPR genes between ADHD and normal controls. The patient with 5-HTTLPR homozygous genotypes of the short allele （ S/S ） had higher CBCL withdrawal and somatic complaints scores than the patients with the heterogenous genotypes of S/L and L/L （ P 〈 0. 05 ）. In the children lacking the 3-repeat allele of DRD4 gene, the subjects with the long 5-HTTLPR allele had a significantly higher score of attentionproblems （10. 4 ±3. 1） and social problems （7.2±3.7） than the subjects with the short allele （8.7±3. 1 and 5.3± 2. 3, respectively ） （ P 〈 0. 05 ）. Conclusion No association between DRD4 and 5-HTTLPR polymorphisms and ADHD is found, but the DRD4 and 5-HTTLPR gene polymorphisms may be related to some ADHD symptoms （attention problems and social problems）.