基因的多态性及其交互作用对儿童注意缺陷多动障碍的影响

Evaluation of potential gene-gene interaction on attention deficit hyperactivity disorder in children

目的探讨5-HTTLPR、5-HT2A受体基因(5-HTR2A)T102C多态性、多巴胺β羟化酶基因(DβH)5'侧翼区-1021C/T多态性及其交互作用对儿童注意缺陷多动障碍(ADHD)的影响,为ADHD儿童的干预与治疗提供理论依据。方法对包头市某小学确诊为ADHD的78例儿童和87名对照组儿童应用PCR-限制性片段长度多态性(PCR-RFLP)方法检测5-HTTLPR、5-HTR2A的T102C多态性及DβH5'侧翼区-1021C/T多态性,采用χ2检验分析3种基因多态性对ADHD的影响,运用Logistic回归分析基因-基因交互作用。结果 5-HTR2A的T102C的基因型频率在ADHD组与对照组间差异有统计学意义(χ2=5.28,P=0.02),5-HTTLPR、DβH5'侧翼区-1021C/T的基因型频率在两组间差异无统计学意义(χ2值分别为0.24,0.01,P值均>0.05);5-HTR2A的T102C基因位点的突变型发生儿童ADHD的危险性是野生型的2.17倍,5-HTR2A的T102C基因位点的突变型分别与5-HTTLPR的S等位基因DβH5'侧翼区-1021C/T基因位点的突变型、共同作用发生儿童ADHD的危险性是单一野生型的2.00,2.80倍。结论 5-HTR2A的T102C的基因型频率在ADHD组与对照组间差异有统计学意义,5-HTTLPR、5-HTR2A的T102C多态性及DβH5'侧翼区-1021C/T多态性在儿童ADHD的发生中存在交互作用。

Objective To evaluate the influence of gene-gene interaction among 5-HTYLPR, 5-HT2A receptor polymor-phism and DI3H-1021C/T polymorphism on attention deficit hyperactivity disorder in children. Methods Polymerasechain reaction （PCR） and RFLP technique were used to test 5-HTFLPR, 5-HT2A receptor T102C polymorphism and DI3H-1021C/T poly- morphism. Chi-square test was used to analyze the influence of gene polymorphism on ADHD. Logistic regression was used to analyze the gene-gene interaction. Results There was significant differences in the frequency of 5-HT2A receptor T102C polymor-phism between ADHD group and controls （X2= 5.28 ,P= 0.02 ） , however, there was no difference in the frequency of 5-HTTLPR, DI3H- 1021C/T polymorphism between ADHD group and controls {X2 = 0.24, P = 0.62 ; χ2 = 0.01, P = 0.93 ）. ADHD was caused by 5-HTR2A T102C mutant than wildtype, ADHD was caused by 5-HTR2A T102C mutant and SL/SS genetype of 5-HTTLPR is 2.00 times than wildtype and L/L genetype of 5-HTTLPR, ADHD was caused by 5-HTR2A T102C mutant and DI3H-1021C/T mutant is 2.80 times than wildtype. Conclusion 5-HTR2A TI02C polymorphism is associated with ADHD. The gene-gene interaction among 5-HTI＇LPR, 5-HTR2A T102C polymorphism and DI3H-1021C/T polymorphism has possible influence on ADHD.