儿童注意缺陷多动障碍与5-羟色胺R2A基因多态性的相关性研究

摘要

Objective To investigate the association between 5-HT R2A gene single nucleotide polymorphisms and attention deficit hyperactivity disorder( ADHD)in children. Methods By random number table method,we enrolled 158 ADHD children as case group,from ADHD children found in the ADHD epidemiological sampling survey among children in Guangxi Province conducted from December 2011 to January 2013. We also enrolled 159 children without ADHD with matching genders and ages among normal population in the same residential areas of children with ADHD as control group. From each subject,5 ml peripheral venous blood was sampled,and DNA was extracted. According to the data about SNPs in the 5-HT R2A gene of Chinese provided by HapMap and relevant literature published at home and abroad,we selected 14 SNPs and designed primer sequence. After PCR amplification,genotypes were determined at the reaction endpoint. Results Case group and control group were significantly different in the genotype distribution of rs2770304,rs985934 and rs6311 locus;case group was higher in the frequency of CC/ CT genotype and lower in the frequency of TT genotype than control group( P < 0. 05). Case group was higher than control group in the frequency of alleles associated with rs2770304,rs985934,rs4941573,rs2070040,rs6313 and rs6311 locus(P < 0. 05). Strong linkage disequilibrium existed among rs1745837,rs3742279 and rs2296972 locus(D' and r2 were both larger than 0. 95 ),among rs2770304,rs985934 and rs4941573 locus,among rs2070040,rs6313 and rs6311 locus. Case group was higher in the haplotype frequency of CCA and ACC and lower in the frequency of haplotype TTG and GTT than control group( P < 0. 05). Conclusion The polymorphism of rs2770304,rs985934,rs4941573,rs2070040,rs6313 and rs6311 locus and haplotype CCA,ACC,TTG and GTT of 5-HT R2A gene may be correlated with ADHD in children.%目的：探讨5-羟色胺（5-HT）R2A 基因单核苷酸多态性与儿童注意缺陷多动障碍（ADHD）的关系。方法于2011年12月—2013年1月广西儿童 ADHD 流行病学抽样调查筛查出的 ADHD 患儿中，采用随机数字表法选取158例为病例组，另在与 ADHD 患儿同一聚居区非 ADHD 者中选择性别、年龄匹配的159例为对照组。取外周静脉血5 ml，提取 DNA。根据 HapMap 提供的存在于中国人群5-HT R2A 基因的单核苷酸多态位点（SNPs）数据，及国内外相关文献，选择14个 SNPs 进行研究，并设计引物序列。PCR 扩增，于反应终点判读基因型。结果病例组与对照组 rs2770304、rs985934和 rs6311位点的基因型分布不同，病例组 CC/ CT 基因型频率高于对照组，TT 基因型频率低于对照组，差异有统计学意义（P ＜0.05）。病例组 rs2770304、rs985934、rs4941573、rs2070040、rs6313和 rs6311位点关联等位基因频率高于对照组，差异有统计学意义（P ＜0.05）。rs1745837、rs3742279和 rs2296972位点两两间存在强连锁不平衡（D＇和 r2均大于0.95），rs2770304、rs985934和 rs4941573位点两两间存在较强连锁不平衡，rs2070040与rs6313、rs6311位点存在较强连锁不平衡。病例组单体型 CCA、ACC 频率高于对照组，单体型 TTG、GTT 频率低于对照组，差异均有统计学意义（P ＜0.05）。结论5-HT R2A 基因 rs2770304、rs985934、rs4941573、rs2070040、rs6313和 rs6311位点多态性及单体型 CCA、ACC、TTG、GTT 可能与儿童 ADHD 的发生有关。