基础医学与临床 ›› 2016, Vol. 36 ›› Issue (7): 1004-1009.

• 研究论文 • 上一篇    下一篇

藏族人群原发性高血压易感基因全基因组关联分析

李广平1,张红心1,邱长春2   

  1. 1. 唐山市工人医院
    2. 中国医学科学院 北京协和医学院
  • 收稿日期:2016-04-11 修回日期:2016-05-21 出版日期:2016-07-05 发布日期:2016-06-22
  • 通讯作者: 邱长春 E-mail:changchunqiu@163.com
  • 基金资助:
    “十一五”科技支撑计划项目

Genomewide association analysis of essential hypertension in Tibetan population

  • Received:2016-04-11 Revised:2016-05-21 Online:2016-07-05 Published:2016-06-22

摘要: 目的 通过全基因组关联分析(GWAS)发现并鉴定与藏族高血压关联的遗传变异。方法 结合高通量芯片分析和高效DNA混合池策略的SNP-MaP方法,对藏族原发性高血压(EH)患者与藏族正常对照进行了全基因扫描。筛选出有显著差异的位点后,用直接测序和PCR-RFLP的方法,进行群体验证,鉴定出各个基因型和相应等位基因的频率。结果 在全基因组的遗传标记中,5个标签位点的等位基因频率在患者组与对照组之间存在显著差异(P <9.2×10-8)。用直接测序和PCR-RFLP的方法进行群体验证,发现rs17136827和rs1866525两个位点的基因型和等位基因频率分布在两组间均无差异;rs 9865108、rs 12541835和rs 4547758的基因型频率和等位基因频率在两组间的差异显著,携带C等位基因个体具有较高的 EH 发病风险。结论 证实affymetrix Human SNP芯片和高效混合池策略结合的SNP-MaP能够有效地大范围分析人类EH易感基因。rs 9865108、rs12541835和rs 4547758与藏族EH易感相关。

关键词: 基因芯片, 全基因组关联分析, 单核苷酸多态性, 混合池

Abstract: Objective To discover and identify genetic variants associated with hypertension through using genomewide association study (GWAS). Methods Using a approach which we called SNP-MaP (SNP microarrays and pooling), We conducted a GWAS to explore the association between multigenic polymorphisms and the development of EH in patients with essential hypertension and health controls in Tibetan population from Lhasa. In this study, DNA from patients or controls were pooled and genotyped using an affymetrix genechip array 6.0. After detected the SNP locus, the SNP frequencies were found in patients and controls respectively by sequencing or PCR-RFLP. The relationship between SNPs and EH was analyzed. Results 5 sequence tagged sites met the genomic criteria of P<9.2×10-8 after Bonferroni correction among whole-genome genetic markers. The differences of genotypes and alleles frequency distributions of the 5 SNP locus was detected by sequencing or PCR-RFLP. The results show that differences of rs17136827 and rs1866525 genotypes and alleles frequency distributions between essential hypertension and healthy controls were not statistically significant, and differences of rs 9865108, rs12541835 and rs 4547758 genotypes and alleles frequency distributions between essential hypertension and healthy controls were statistically significant in population. Conclusions Our results demonstrate that affymetrix human SNP microarrays and pooling provide a very effective platform for genome-wide analysis of SNPs which are susceptible to essential hypertension. The polymorphisms of SNPs(rs 9865108, rs12541835 and rs 4547758 ) are associated with essential hypertension in Tibetan population.

Key words: Gene chip, GWAS, SNP, Pooling

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