Racial differences in microRNA and gene expression in hypertensive women.

Racial differences in microRNA and gene expression in hypertensive women.
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DOI:
10.1038/srep35815
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发表时间:
2016-10-25
期刊:
影响因子:
4.6
通讯作者:
Evans MK
Evans MK
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Dluzen DF;Noren Hooten N;Zhang Y;Kim Y;Glover FE;Tajuddin SM;Jacob KD;Zonderman AB;Evans MK

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系统性动脉高压是心血管疾病发病率和死亡率的重要原因。非裔美国人受高血压的影响不成比例,事实上,高血压的发病率、患病率和严重程度在非裔美国人(AA)女性中最高。先前的数据表明,差异基因表达影响个体对所选疾病的易感性,我们假设这种现象可能会影响高血压的健康差异。对再生障碍性贫血或白人、血压正常或高血压女性外周血单个核细胞的转录图谱鉴定出数千个因种族和/或高血压而差异表达的mRNAs。与正常血压或白色高血压患者相比,女性AA高血压患者的主要基因表达存在差异。由于microRNAs在基因表达调控中起着重要作用,我们分析了全球microRNA的表达情况,并观察到RACE和/或高血压患者差异表达的microRNAs。我们发现了可能参与高血压相关通路的新的mRNA-microRNA对,并且存在差异表达,包括MCL1/miR-20a-5p、APOL3/miR-4763-5p、PLD1/miR-4717-3p和PLD1/miR-4709-3p。我们通过RT-qPCR验证了基因表达水平,并在原代内皮细胞中进行了microRNA靶标验证。总之,我们确定了AA和白人女性高血压患者之间显著的基因表达差异,并精确定位了高血压和种族差异表达的新的mRNA-microRNA对。这些差异可能导致已知的高血压差异,并可能成为干预的潜在目标。
Systemic arterial hypertension is an important cause of cardiovascular disease morbidity and mortality. African Americans are disproportionately affected by hypertension, in fact the incidence, prevalence, and severity of hypertension is highest among African American (AA) women. Previous data suggests that differential gene expression influences individual susceptibility to selected diseases and we hypothesized that this phenomena may affect health disparities in hypertension. Transcriptional profiling of peripheral blood mononuclear cells from AA or white, normotensive or hypertensive females identified thousands of mRNAs differentially-expressed by race and/or hypertension. Predominant gene expression differences were observed in AA hypertensive females compared to AA normotensives or white hypertensives. Since microRNAs play important roles in regulating gene expression, we profiled global microRNA expression and observed differentially-expressed microRNAs by race and/or hypertension. We identified novel mRNA-microRNA pairs potentially involved in hypertension-related pathways and differently-expressed, including MCL1/miR-20a-5p, APOL3/miR-4763-5p, PLD1/miR-4717-3p, and PLD1/miR-4709-3p. We validated gene expression levels via RT-qPCR and microRNA target validation was performed in primary endothelial cells. Altogether, we identified significant gene expression differences between AA and white female hypertensives and pinpointed novel mRNA-microRNA pairs differentially-expressed by hypertension and race. These differences may contribute to the known disparities in hypertension and may be potential targets for intervention.
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