DNA混合池技术全基因组关联研究筛查主动脉夹层易感基因的研究

目的筛选主动脉夹层发病机制相关的遗传易感基因。方法选取主动脉夹层患者为病例组（150例），按照性别、年龄、是否吸烟、合并高血压、糖尿病情况与病例组匹配的原则入选排除主动脉夹层、重大心血管疾病及肿瘤的志愿者为对照组（250例），均从外周血提取基因组DNA，采用DNA混合池技术为基础的Illumina Human660W—Quad芯片扫描，筛选主动脉夹层发病相关的遗传易感基因。结果对照组女性数量明显多于病例组（P〈0．01）；在年龄、吸烟、高血压、糖尿病人数方面差异均无统计学意义（P〉0．05）。根据芯片扫描结果，挑选silhouettewidth计算值大于0．7，最小等位基因频率（MAF）大于0．05，且SNPs位于已知名称基因上的前5个SNPs位点。结果发现，遗传变异位点SNP rs2970873（位于PPARGClA基因）、SNP rs12678080（位于SGCZ基因）、SNP rs489526（位于UNCl3C基因）、SNP rs6928665（位于TRAM2基因）和SNP rs17837003（位于ACCNl基因上）可能与主动脉夹层的发病机制有关。结论SNPsrs2970873、rs12678080、rs489526、rs6928665和rsl7837003可能与主动脉夹层发病机制相关。

Identification of susceptibility genes for aortic dissection using pooling-based genomewide association scans

Objective To identify novel susceptibility loci for aortic dissection. Methods 150 patients with aortic dissection were involved as case group and 250 volunteers as control group. Illumina Human660W-Quad v1.0 DNA Analysis BeadChip Kit with DNA pooling was used in the screening stage, and 5 high-ranked single nucleotide polymorphisms （SNPs） were included in this panel. Results Results showed that the number of women in the control group was significantly more than that in the case group （P〈0.01）. There was no statistical significant difference in the age, smoking, hypertension and diabetes population （P〉0.05）. Variants SNPs rs2970873 in the PPARGC1A gene, rs12678080 in the SGCZ gene, rs489526 in the UNC13C gene, rs6928665 in the TRAM2 gene and rs17837003 in the ACCN1 gene may be related to the incidence of aortic dissection. Conclusions Pooling-based genome-wide association scans has been shown to be a cost-efficient way to select candidate susceptibility loci. Variants SNPs rs2970873, rs12678080, rs489526, rs6928665 and rs17837003 were found having increased susceptibility with aortic dissection.