Chinese Journal of Stroke ›› 2016, Vol. 11 ›› Issue (04): 269-276.

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Study on the Correlation between HDAC9 Gene SNPs and Large Vessel Atherosclerosisinduced Ischemic Stroke  

1 350122 福州福建中医药大学康复医学院
2 福建省运动功能康复重点实验室
3 福建中西医结合研究院
4 美国俄克拉荷马州立大学健康医学中心   

  • Received:2015-08-11 Online:2016-04-20 Published:2016-04-20

HDAC9基因SNPs与大动脉粥样硬化缺血性卒中的相关性研究

柳维林,林云娇,陶静,彭军,李光谱,陈立典   

  1. 1 350122 福州福建中医药大学康复医学院
    2 福建省运动功能康复重点实验室
    3 福建中西医结合研究院
    4 美国俄克拉荷马州立大学健康医学中心
  • 通讯作者: 陈立典 cld@fjtcm.edu.cn

Abstract:

Objective To investigate the correlation between histone deacetylase 9 (HDAC9) gene susceptible single nucleotide polymorphisms (SNPs) and genotype and its phenotype in large vessel atherosclerosis-induced ischemic stroke. Methods By using the Haploview software and data on genetics from thousands of human genome project (HapMap) , the analysis of SNPs of HDAC9 gene, minor allele frequency (MAF), single block and haplotype and tag SNPs were performed. Results A total of 75 SNPs in the Chr7:18930kb--19020kb regions of HDAC9 gene were determined, of which 51 SNPs accorded with Hardy-Weinberg balance (P >0.05), and MAF (P >0.05). Based on the confidence intervals, four Gamete rule and solid spine of LD, the 11, 14 and 8 single domains were constructed, respectively. Among which, the rs2717356 site was low linkage disequilibrium (LD) and outside of the single domain belonging to HDAC9 gene recombination hotspots. A total of 30 SNPs were determined as haplotype tagging SNPs (htSNPs) according with R2 was more than or equal to 0.8, and LOD was more than or equal to 3.0, and that showed MAF was more than 0.10. The rs2526630 [C/T] site located in HDAC9 3 'UTR region, binding with microRNAs like hsa-miR-545, hsa-miR-616, etc. Conclusion The 30 htSNPs served as reference for HDAC9 gene susceptibility SNP sites for screening and validating repeatedly. The binding of rs2526630 site of HDAC9 gene and miRNA might associate with the morbidity of large vessel atherosclerosis-induced ischemic stroke.

Key words: HDAC9 gene; SNPs; Ischemic stroke

摘要:

目的 探讨组蛋白去乙酰化酶9(histone d eacetylase 9,HDAC9)在动脉粥样硬化缺血性卒中易感区 域单核苷酸多态性(single nucleotide polymorphisms,SNPs)与基因型和生物学表型的相关性。 方法 利用Haploview软件和千人基因组计划提供的遗传学数据,对HDAC9基因SNPs位点的最小等 位基因频率(minor allele frequency,MAF)、单体域和单体型以及标签SNPs(haplotype tagging SNPs, htSNPs)进行分析。 结果 在HDAC9基因Chr7:18930kb-19020kb区域共测定75个SNPs,其中Hardy-Weinberg平衡P >0.05, 且MAF P >0.05的SNPs共51个。基于confidence intervals,four Gamete rule和solid spine of LD算法分别构 建了11、14和8个单体域,其中rs2717356位点连锁不平衡程度低,且不在单体域内,属于HDAC9基因 的重组热点区域。取r 2≥0.8,且LOD值≥3.0确定30个SNPs为htSNPs,且MAF均大于0.10;在htSNPs中发 现rs2526630位点[C/T]位于HDAC9的3'UTR区域,与hsa-miR-545,hsa-miR-616等microRNAs结合。 结论 30个标签htSNPs作为人群HDAC9基因易感SNPs位点筛查和重复验证的依据。HDAC9基因 rs2526630位点影响与miRNA的结合在动脉粥样硬化缺血性卒中的发病中可能相关。

关键词: HDAC9基因; SNPs; 缺血性卒中