MicroRNA expression in abdominal and gluteal adipose tissue is associated with mRNA expression levels and partly genetically driven.

MicroRNA expression in abdominal and gluteal adipose tissue is associated with mRNA expression levels and partly genetically driven.
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DOI:
10.1371/journal.pone.0027338
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发表时间:
2011
期刊:
影响因子:
3.7
通讯作者:
Lindgren CM
Lindgren CM
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Rantalainen M;Herrera BM;Nicholson G;Bowden R;Wills QF;Min JL;Neville MJ;Barrett A;Allen M;Rayner NW;Fleckner J;McCarthy MI;Zondervan KT;Karpe F;Holmes CC;Lindgren CM

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为了了解miRNA如何影响脂肪组织的分子表型和相关性状,我们在70名人类受试者的皮下腹部和臀部脂肪组织中进行了总体miRNA表达谱分析,并表征了哪些miRNA在这些组织之间差异表达。我们发现,在初步研究中,12%的miRNAs在腹部和臀部脂肪组织之间显著差异表达(FDR校正的p<0.05),其中59个在40个额外受试者的随访研究中重复。此外,发现14种miRNA与腹部组织中的代谢综合征病例对照状态相关,并且其中三种是重复的(初步研究:FDR校正的p<0.05,重复:p<0.05和方向一致的效果)。在70名受试者中进行全基因组基因分型,以进行miRNA表达数量性状位点(eQTL)分析。在另外40名受试者中对候选miRNA eQTL进行随访,并鉴定出6个显著的独立顺式定位的miRNA eQTL(初步研究:p<0.001;重复:p<0.05和方向一致效应)。最后,在两种组织中进行全局mRNA表达谱分析,以实现miRNA和靶mRNA表达水平之间的关联分析。我们发现腹部脂肪组织中有22%的miRNA,臀脂肪组织中有9%的miRNA,其表达水平与相应靶mRNA的表达显着相关(FDR调整后p<0.05)。总之,我们的研究结果表明,腹部和臀部脂肪组织的miRNA分子表型谱存在明显差异,一些miRNA的表达受到顺式定位遗传变异的影响,并且miRNA与其预测的mRNA靶点的表达水平相关。
To understand how miRNAs contribute to the molecular phenotype of adipose tissues and related traits, we performed global miRNA expression profiling in subcutaneous abdominal and gluteal adipose tissue of 70 human subjects and characterised which miRNAs were differentially expressed between these tissues. We found that 12% of the miRNAs were significantly differentially expressed between abdominal and gluteal adipose tissue (FDR adjusted p<0.05) in the primary study, of which 59 replicated in a follow-up study of 40 additional subjects. Further, 14 miRNAs were found to be associated with metabolic syndrome case-control status in abdominal tissue and three of these replicated (primary study: FDR adjusted p<0.05, replication: p<0.05 and directionally consistent effect). Genome-wide genotyping was performed in the 70 subjects to enable miRNA expression quantitative trait loci (eQTL) analysis. Candidate miRNA eQTLs were followed-up in the additional 40 subjects and six significant, independent cis-located miRNA eQTLs (primary study: p<0.001; replication: p<0.05 and directionally consistent effect) were identified. Finally, global mRNA expression profiling was performed in both tissues to enable association analysis between miRNA and target mRNA expression levels. We find 22% miRNAs in abdominal and 9% miRNAs in gluteal adipose tissue with expression levels significantly associated with the expression of corresponding target mRNAs (FDR adjusted p<0.05). Taken together, our results indicate a clear difference in the miRNA molecular phenotypic profile of abdominal and gluteal adipose tissue, that the expressions of some miRNAs are influenced by cis-located genetic variants and that miRNAs are associated with expression levels of their predicted mRNA targets.
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