摘要
目的探讨心脏发育相关基因PITX2与间隔缺损类先天性心脏病（CHD）的相关性。方法综合美国国立生物技术信息中心网站（NCBI）dbSNPs数据库和SNPper软件的检索结果，确定所要研究的单核苷酸多态性（SNPs）位点。病例组30例间隔缺损类CHD患儿及对照组30例儿童，取其静脉血行PITX2基因目的片段DNA直接测序。分析各SNPs位点的等位基因、基因型在病例组和对照组间分布频率的统计学差异。结果确定PITX2基因2个SNPs位点分别为rs1051887和rs28936409，rs1051887：编码核苷酸序列第954位的鸟嘌呤变为胞嘧啶，导致第106位的谷氨酸变为谷氨酰胺；rs28936409：编码核苷酸序列第910位的鸟嘌呤变为胞嘧啶，导致第91位的精氨酸变为脯氨酸，所选2个SNPs在病例组及对照组中均未见多态性结果。首次发现了PITX2基因的304C〉G（Glu102Gln）位点存在C／G基因型，病例组的cG基因型频率高于对照组（x2=8．531，P〈0．05），等位基因的频率亦高于对照组（X2=6．508，P〈0．05），cG基因型使间隔缺损类CHD发生的危险度增加（CG基因型的OR=2．833，95％CI：1．297～6．188）。病例组及对照组的基因型分布经Hardy—Weinberg遗传平衡检测差异无统计学意义（P〉0．05）。结论本研究首次发现P1TX2基因新的SNP位点304C〉G（Glu102Gln），其CG基因型可能使间隔缺损类CHD的发病危险性增加。
Objective To investigate the correlation between heart development related genes paired-liked homeodomain transcription factor 2 （PITX2） and interval defect congenital heart disease（CHD）. Methods To target the investigated single nucleotide polymorphisms （SNPs） by means of dbSNPs data base of National Center of Biotechnology Information（NCBI） website and online bioinformatics software,SNPper. To compared SNPs using 30 interval defect CHD patients and 30 healthy children as control group. Venous blood were collected to detect PITX2 DNA sequencing, then new SNPs were explored. Statistic differences of alleles and genotype frequency distribution between case group and control group were analyzed sequentially. Results Two SNPs in PITX2 genes were rs1051887 and rs28936409, rs1051887 ：a substitution of cytosine for guanine at nucleotide 954,which suggested the conversion of glutamic acid into glutamine at amino acid residue 106 ;rs28936409 ：a substitution of cytosine for guanine at nucleotide 910, which suggested the conversion of arginine into proline at amino acid residue 91. The selected 2 SNPs in the case group and control group showed no polymorphism results. In this research,a new polymorphism 304C 〉 G（Glu102Gln） in PITX2 gene was first identified. Frequencies of CG genetype in case group were higher than control group（x2 = 8. 531, P 〈 0.05 ） , and similar results were found in alleliefrequencies （X2 = 6.508, P 〈 0.05 ）. Accordingly, CG genetype increased the risk of interval defect CHD（ CG genetype OR = 2. 833,95% CI： 1. 297 - 6. 188 ）. Moreover, data showed there was no significant difference in the genotype distribution of SNPs between the case group and control group via Hardy-Weinberg Testing（P 〈 0.05 ）. Conclusions A new SNP 304C 〉 G（Glu102Gln） was found and the CG genetype of the new SNP （304C 〉 G） may increase the risk of interval defect CHD.
出处
《中华实用儿科临床杂志》
CAS
CSCD
北大核心
2014年第1期24-27,共4页
Chinese Journal of Applied Clinical Pediatrics
基金
基金项目：天津市卫生局科技基金项目（2010KZ35）
关键词
先天性心脏病
PITX2基因
单核苷酸多态性
等位基因
基因型频率
Congenital heart disease
Paired-liked homeodomain transcription factor 2 gene
Single nucleotide polymorphisms
Allelic gene
Genotype frequency
