摘要
目的研究多巴胺D4受体(DRD4)基因第3外显子48bp可变数串联重复序列多态性(VNTR)与注意缺陷多动障碍(ADHD)的易患性是否存在相关。方法采用聚合酶链式反应(PCR)技术,检测ADHD患者及其父母和正常对照者DRD4基因48 bpVNTR,分析其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(TDT、HHRR)方法分别进行分析。结果在广西地区汉族309人中,DRD4基因第3外显子48 bpVNTR存在6种等位基因、8种基因型。在广西地区汉族35例ADHD患儿中,发现3种DRD4等位基因,4种基因型。病例-对照关联分析结果表明:DRD4基因第3外显子48 bpVNTR与ADHD无关(χ2=6.126,df=5,P=0.294)。核心家系的关联分析表明2*等位基因(χ2=0.129,P>0.005)、4*等位基因(χ2=0.129,P>0.05)与ADHD的易患性无关。病例对照分析,表明DRD42*等位基因(χ2=0.43,P>0.05)、4*等位基因(χ2=0.20,P>0.05)与ADHD不存在连锁不平衡。结论在中国广西地区汉族人群中存在DRD4×7等位基因。中国广西地区汉族人群中DRD4基因第3外显子48 bpVNTR的基因频率分布以DRD4×4最常见,与国内外报道的亚洲人群中的频率分布一致。在广西地区,DRD4基因第3外显子48 bpVNTR多态性与ADHD的易患性无相关。
[Objective] To investigate the distribution frequency of 48bp VNTR polymorphism at exon 3 of dopamine D4 receptor （DRD4） gene in Han nationality Guangxi province and the relationship between attention deficit hyperactivity disorder （ADHD） children and a 48 bp repeat polymorphism in exon 3 of the dopamine receptor D4 gene. [Methods] The diagnosis was ascertained according to DSM-IV criteria. DNA was extracted directly from blood lymphocytes. DRD4 48-bp VNTR allele and genotype frequencies were examined by PCR amplification. The Hardy-Weinberg equilibrium was calculated using the allele frequency. Association of polymorphisms and ADHD children were examined by comparing patients and control cases and using family-based association study in an extension of transmission disequilibrium test （TDT） and haplotype-based haplotype relative risk （HHRR）. [Results] Our study showed： In control group the repeat numbers of 48 bp VNTR polymorphism at exon 3 of dopamine D4 receptor （DRD4） gene were 2 to 7 and 4-repeat allele detected was the dominant allele of DRD4 gene at exon 3 polymorphisms with the allele frequency 0.599. Eight kinds of genotype were detected and the genotype 4＊/2＊ was the most common genotype with genotype frequency at 0.43. In patient group the repeat numbers of 48 bp VNTR polymorphism at exon 3 of DRD4 gene were 2, 4 and 5 and 4-repeat allele detected was the dominant allele of DRD4 gene at exon 3 polymorphisms with the allele frequency at 0.614. Four kinds of genotype were detected and the genotype 4＊/2＊ was the most common genotype with genotype frequency at 0.571. Genotype frequencies of ADHD children and their parents as well as the normal controls were all met the Hardy-Weinberg equilibrium. The frequency distributions of allele and genotype were no significantly difference between ADHD group and control group. No significant association was found between ADHD and 48 bp VNTR polymorphism at exon 3 of dopamine D4 re- ceptor （DRD4） by using HHRR and TDT. [ Conclusion ] Our study showed： DRD4x7 alleles were found to exist among the population of the Han nationality in Guangxi. The gene frequency of DRD4x4 was the most common distribution in 48bp VNTR polymorphism at exon 3 of dopamine D4 receptor （DRD4） in the the crowd of the Han nation- ality of Guangxi district of China, which is stated in the previous reports. Our results did not support previous find- ings that there was an association between ADHD and the DRD4 gene polymerphism.
出处
《中国现代医学杂志》
CAS
CSCD
北大核心
2007年第16期1954-1958,共5页
China Journal of Modern Medicine
