中文摘要：

目的对法洛四联症（TOF）患儿类视黄酸受体d（RXRA）基因启动子区序列进行分析，探讨RXRA基因变异与TOF的关联性。方法采取病例对照研究方法，以2007年4月至2012年12月心导管检查及外科手术证实为TOF患儿为TOF组，以同时期年龄和性别与TOF组匹配的健康儿童为对照组。采集静脉血，提取基因组DNA，PCR扩增RXRA基因转录起始位点（TSS）上游1417bp的启动子区序列，扩增产物采用ABIPrismBigdye系统进行测序。结果TOF组纳入213例（男135例，女78例），平均年龄1．8岁；对照组纳入500名（男310名，女190名），平均年龄2．5岁。①nXnA基因TSS上游1191bp处检测出1个杂合突变，即-1191A〉AG（TSS定为＋1）；检测出3个新发SNP，即-1287C〉CT、-800C〉CA及-760C〉CT。②利用http：／／www．cbrc．jp／research／db／TFSEARCH．html网站进行分析，发现在该4个位点及其附近有多个转录因子结合位点。-1191A〉AG导致新的CpG位点产生，-800C〉CA导致原有CpG位点消失。这些新产生的CpG位点的甲基化可能会影响转录因子的结合，从而影响RXRA基因转录水平，进一步导致RXRA蛋白水平的变化。结论TOF患儿RXRA基因启动子区序列变化可能通过影响RXRA表达水平而导致TOF的发生。

英文摘要：

Objective Congenital heart disease （CHD） is the most common birth defect in humans. The genetic causes for CHD remain largely unknown. Tetralogy of Fallot （TOF） is one major component of conotruncal defects （CTD） , a complex CHD induced by abnormal development of the outflow tract. Retinoid X receptor alpha （RXRA） , a ligand-dependent transcript factor, plays a critical role in muhiple aspects of cardiogenesis including the development of outflow tract （OFT）. Taken together, RXRA may be a potential candidate gene of TOF. To date, RXRA gene promoter region has not been analyzed and reported in TOF patients. We hypothesized that the sequence variants within RXRA gene promoter region may change RXRA levels and the development of TOF. In this study, the promoter regions of RXRA gene were genetically analyzed. Methods Case group included DNA samples from patients with TOF, which had been confirmed by cardiac catheterization and surgery. Control group consisted of DNA samples from randomly selected healthy children. Genomic DNA was extracted from peripheral blood. PCR was used to amplify the 1 417 bp promoter region from genomic DNA. PCR products were sequenced by ABI Prism Bigdye system. Results The promoter regions of RXRA gene were genetically analyzed in 213 TOF patients and 500 healthy controls. One novel heterozygous mutation, - 1 191A 〉 AG （according to the transcription start site）, was found in one TOF patients, but in none of controls. Three novel single-nucleotide polymorphisms, - 1287C 〉 CT, - 800C 〉 CA and - 760C 〉 CT were found in both TOF patients and controls. There were no statistically significant changes in the genotype and allele frequencies of the three SNPs between TOF patients and control group （ P 〉 0.05 ）. Several transcription factor binding sites were found within the region containing these single-nucleotide variations by searching http ：//www. cbrc. jp/research/db/TFSEARCH, html. Conclusions The A at position -1 191 following C, and C at position -800