摘要
目的探讨色氨酸羟化酶2(TPH2)基因的单核苷酸多态性(SNP)位点rs11178997和rs4570625多态性与注意缺陷多动障碍(ADHD)之间的关系。方法根据美国《精神障碍诊断与统计手册》4版中ADHD诊断标准,选择45例ADHD患儿和90例健康儿童分别作为研究组和对照组。优化基因芯片杂交技术,设计并合成2个突变位点rs4570625和rs11178997的探针和2对丙烯酰胺标记的引物;样本经PCR扩增后,采用丙烯酰胺点样液制备芯片,并与TEMED反应固定芯片;分别用探针与芯片杂交,采用扫描仪分析研究组和对照组儿童的TPH2的SNPs多态性位点rs4570625和rs11178997的基因型频率。结果研究组TPH2基因SNP位点rs4570625的T/T基因型频率明显多于对照组[χ2=4.688P=0.030,OR(T/T)=2.333,95%CI1.074～5.071];研究组TPH2基因SNP位点的T等位基因频率明显高于对照组[P=0.031,OR(T)=1.761,95%CI1.050～2.952]。研究组TPH2基因的SNP位点rs11178997的A/T基因型频率明显多于对照组[χ2=3.888P=0.049,OR(A/T)=2.129,95%CI0.998～4.542],2组基因型A/A和T/T频率分布差异无统计学意义;2组的等位基因频率差异均无统计学意义。研究组TPH2基因SNP位点rs11178997和rs4570625位点AT-TT联合型频率高于对照组,2组比较有统计学差异[χ2=3.985P=0.046,OR(AT-TT)=3.027,95%CI0.981～9.342]。结论rs4570625基因型纯合子T/T与ADHD可能相关,rs4570625的T等位基因可能是ADHD的易感基因。rs11178997和rs4570625位点基因型AT-TT联合型可能增加了ADHD的患病风险。
Objective To explore the association between signal nucleotide polymorphisms（SNP）of the gene encoding tryptophan hydroxylase 2（TPH2）and attention deficit hyperactivity disorder（ADHD）.Methods Forty-five ADHD children ascertained according to the Diagnostic and Statistical Manual of Mental Disorders（the 4th edition）were included as the study group,and 90 healthy children were included as the control group.The gene chip hybridization technique was optimized and 2 primers modified by acrylamide were designed.The probes of rs4570625 and rs11178997 were designed.After the polymerase chain reaction（PCR）was conducted,the product of PCR was mixed with application of sample including acrylamide,which was fixed to glass through reaction to tetramethylethylenediamine.After the probes were hybridized with PCR product,the different genotype could be scanned and identified through scanning apparatus.All subjects＇ genotypes of polymorphism of TPH2 geners11178997 and rs4570625 were identified with the gene chip hybridization technique.The allelic and genotypic distributions of the 2 SNPs were compared among patients with ADHD and controls to explore the association between ADHD and 2 SNPs of TPH2：rs4570625 and rs11178997.Results Significant association was found between T/T homozygote and ADHD [χ2=4.688 P=0.030,OR（T/T）2.333,95%CI 1.074-5.071].There was also significant association between T allele and ADHD [P=0.031,OR（T）=1.761,95%CI 1.050-2.952].Significant association was also found between A/T heterozygote and ADHD [χ2=3.888 P=0.049,OR（A/T）=2.129,95%CI 0.998-4.542].But associations between A/A,T/T homozygote and ADHD were not found,nor between alleles and ADHD.Combined risk analysis of SNPs rs11178997 and rs4570625 in the total sample demonstrated significant associations of ADHD and AT-TT combined genotype in which the number of AT-TT combined genotype was more in ADHD patients compared with controls subjects [χ2=3.985 P=0.046,OR（AT-TT）=3.027,95%CI 0.981-9.342].Conclusions The homozyg
出处
《实用儿科临床杂志》
CAS
CSCD
北大核心
2009年第24期1878-1881,共4页
Journal of Applied Clinical Pediatrics
基金
卫生部科研基金项目资助(20090103)
河南省教育厅自然科学基金项目资助(611042800,2008A320006)
关键词
注意缺陷多动障碍
色氨酸羟化酶2
单核苷酸多态性
attention deficit hyperactivity disorder
tryptophan hydroxylase 2
single nucleotide polymorphisms
