多巴胺D4受体基因多态性与原发性夜间遗尿症的关联研究

Relationship between dopamine D4 receptor gene polymorphisms and primary nocturnal enuresis

目的研究多巴胺D4受体(dopamine D4 receptor,DRD4)基因的多态性及其组合分布与原发性夜间遗尿症(PNE)的相关性。方法选取无亲缘关系的PNE儿童86例以及无亲缘关系的健康儿童100例为对照组,提取静脉血白细胞基因组DNA,采用聚合酶链反应及等位基因特异性扩增技术检测DRD4基因-1240L/S,-521C/T与-616C/G3个位点的基因型。结果PNE组与对照组DRD4-616C/G的等位基因频率及基因型频率差异存在显著性(χ2=8.13,P<0.05;χ2=6.23,P<0.05)。等位基因组合分布研究发现DRD4-1240L/S-616C/G-521C/T组合的单倍型LCT分布频率在PNE组明显高于正常对照组(χ2=5.88,P<0.05)。结论PNE儿童DRD4基因-616位点由G到C的转换可能影响DRD4基因的诱导及转录,DRD4基因启动子区3个功能多态位点构成的单倍型LCT可能进一步协同抑制了DRD4基因的转录活性,可能使DRD4蛋白表达降低,注意力缺陷,睡眠觉醒障碍,引起夜间遗尿。

Objective To study polymorphisms of dopamine 134 receptor （DRD4） in children with primary nocturnal enuresis （PNE） and explore the relationship between DRD4 gene polymorphisms and PNE. Methods Genomic DNA was isolated from leukocytes in 86 unrelated children with PNE and in 100 healthy unrelated children （controls）. Polymorphisms of DRD4-1240L/S, -616C/G and -521C/T were genotyped by allele-specific primer PCR. Results There were significant differences in allele frequencies （ χ^2 = 8.13, P 〈 0.05 ） and genotypes frequencies （ χ^2 = 6： 23, P 〈0. 05） of DRD4-616C/G between PNE patients and healthy controls. The frequency of haplotype LCT consisting of 3 function polymorphic sites DRD4-1240L/S, -616C/G and -521C/T in PNE patients was statistically higher than that in healthy controls （ χ^2 = 5.88, P 〈 0.05）. Conclusions The change of C to G of DRD4-616 may affect the induction and transcription of DRD4 gene. The haplotype LCT consisting of 3 function polymorphic sites DRD4-1240L/S, -616C/G and -521C/T may synergistically inhibit the transcription activity of DRD4 gene. This might lead to a reduction of DRD4 protein expression and cause noctumal enuresis.