微小RNA-181基因家族单核苷酸多态性和基因表达水平与缺血性脑卒中遗传易感性的关系

雷茗; 谭昙; 黄艳云; 韦叶生

doi:10.16098/j.issn.0529-1356-2022.04.010

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解剖学报 ›› 2022, Vol. 53 ›› Issue (4) : 470-478. DOI: 10.16098/j.issn.0529-1356-2022.04.010

微小RNA-181基因家族单核苷酸多态性和基因表达水平与缺血性脑卒中遗传易感性的关系

雷茗¹ 谭昙¹ 黄艳云² 韦叶生^3*

作者信息 +

Association between the polymorphism and expression level of the family microRNA-181 and susceptibility of ischemic stroke

LEI Ming¹ TAN Tan¹ HUANG Yan-yun² WEI Ye-sheng^3*

Author information +

文章历史 +

摘要

目的探讨微小RNA（miR）-181基因家族rs16927589、rs77418916和rs8108402位点单核苷酸多态性（SNP）与缺血性脑卒中(IS)遗传易感性之间的关系；比较对照组与IS组中miR-181基因家族表达水平的差异，进一步探讨与基因表达水平之间的关系，为IS的防治工作提供帮助。方法使用SNaPshot技术对349例IS患者和372例对照组进行SNP基因分型检测，并用DNA测序法加以验证；使用日立7600生化仪检测对照组和IS组血脂水平；用ABI7500 Real-time PCR仪检测对照组和IS组外周血单核细胞miR-181基因家族的表达水平。结果关于rs8108402位点有CC、CT、TT 3种基因型，对照组和IS组基因型及等位基因频率对比发现，与CC基因型比较，CT基因型的携带人群患IS的风险性明显增高，TT基因型携带者患IS风险降低［CC vs CT:优势比（OR）=1.56,95%置信区间（CI）,1.11~2.18, P<0.05; CC vs TT: OR=0.25,95%CI, 0.10~0.62, P<0.01］，等位基因分析未发现相关性；rs16927589位点检测出TT、CT、CC 3种基因型，rs77418916位点有AA、AT、TT 3种基因型，对照组与IS组对比，未发现相关性。对rs8108402位点分层分析表明，携带CC基因型的IS患者其低密度脂蛋白（LDL-C）比携带CT基因型的IS患者高（P<0.05），rs8108402位点多态性可能与IS的临床表现有相关性。IS组中，外周血单核细胞中miR-181a、miR-181b和miR-181c的表达明显高于对照组，差异有统计学意义（P<0.05），而miR-181d的表达低于对照组，差异无计学意义（P>0.05）；对阳性位点rs8108402位点多态性与基因表达水平进一步分析发现，rs8108402位点多态性与基因表达水平无相关性。结论 MiR-181c基因rs8108402位点CT和TT基因型可增加IS患病风险，CTC单倍型可增加IS患病风险。MiR-181c基因rs8108402位点多态性与LDL-C的高低有相关性，携带CC基因型的IS患者，其LDL-C水平较携带CT基因型患者高。MiR-181基因家族在正常对照组和IS组中的表达有明显差异，miR-181基因家族可能是IS的潜在的预测靶标和治疗靶基因。

Abstract

Objective To explore the association between rs16927589, rs77418916, rs8108402 of the family microRNA(miR)-181 polymorphisms and ischemic stroke(IS)，and compare the expression of miR-181 genes between control group and IS group, further explore the association between polymorphisms and the expression levels of genes, to provide assistance for the prevention and treatment of IS. Methods SNaPshot technique and DNA sequencing were used to examine the single nucleotide polymorphism(SNP) genotypes of 349 patients of IS and 372 controls, serum lipid level was detected by biochemical analyzer 7600; The expression level of miR-181 genes in peripheral blood mononuclear cells of control group and IS group were detected by ABI7500 Real-time PCR. Results The genotype and allele of rs8108402 were compared between the control group and IS group, and it was found that compared with CC genotype, the risk of IS was significantly increased among people with CT genotype, TT genotype was opposite ［CC vs CT：odds ratio(OR)=1.56，95% confidence interval(CI),1.11-2.18,P=0.011;CC vs TT: OR=0.25, 95% CI,0.10-0.62, P=0.003］. However, there were no correlation with IS of rs16927589 and rs77418916 polymorphisms. Stratified analysis of rs8108402 showed that the low-density lipoprotein (LDL-C) of IS patients with CC genotype was higher than that of IS patients with CT genotype (P<0.05), and the polymorphism of rs8108402 might be correlated with the clinical manifestations of IS. In IS group, the expression of miR-181a, miR-181b, miR-181c were obviously higher than that in control group, the difference was statistically significant (P<0.05), while the expression of miR-181d significantly lower than the control group, but the difference was not statistically

significant (P>0.05). Further analysis of rs8108402 polymorphism and gene expression level showed no correlation between rs8108402 polymorphism and gene expression level. Conclusion The CT and TT genotypes at rs8108402 of miR-181c increase the risk of IS, while the CTC haplotype increase the risk of IS. The polymorphism of rs8108402 is correlated with the level of LDL-C. There are significant differences in the expression of miR-181 gene clusters between the normal control group and the IS group, and miR-181 clusters may be potential predictive targets and therapeutic targets of IS.

导出引用

雷茗谭昙黄艳云韦叶生. 微小RNA-181基因家族单核苷酸多态性和基因表达水平与缺血性脑卒中遗传易感性的关系[J]. 解剖学报. 2022, 53(4): 470-478 https://doi.org/10.16098/j.issn.0529-1356-2022.04.010

LEI Ming TAN Tan HUANG Yan-yun WEI Ye-sheng. Association between the polymorphism and expression level of the family microRNA-181 and susceptibility of ischemic stroke[J]. Acta Anatomica Sinica. 2022, 53(4): 470-478 https://doi.org/10.16098/j.issn.0529-1356-2022.04.010

中图分类号： R-394.5

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