Circulating long noncoding RNA GAS5 levels are correlated to prevalence of type 2 diabetes mellitus.
Circulating long noncoding RNA GAS5 levels are correlated to prevalence of type 2 diabetes mellitus.
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DOI：
10.1016/j.bbacli.2015.09.001
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发表时间：
2015-12
期刊：
影响因子：
--
通讯作者：
Patel NA
中科院分区：
文献类型：
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作者：
Carter G;Miladinovic B;Patel AA;Deland L;Mastorides S;Patel NA
糖尿病（DM）是一种代谢性疾病，其特征是空腹血糖水平受损。2型糖尿病是成人发病的糖尿病。长链非编码rna （lncRNAs）调节基因表达，多项研究已将lncRNAs与人类疾病联系起来。96名退伍军人的血清样本保存在研究生物标本库中。我们采用了两阶段策略来确定其水平与T2DM相关的lncRNA。最初，我们使用lncRNA阵列从糖尿病和非糖尿病个体中筛选了5个血清样本。接下来，使用定量PCR分析96份血清样本中GAS5 lncRNA的水平。我们进行受试者工作特征（ROC）分析，以确定诊断糖尿病的最佳临界值GAS5。我们的研究结果表明，在美国退伍军人队列中，血清中GAS5水平降低与糖尿病有关。ROC分析显示最佳截断GAS5值小于或等于10。qPCR结果显示，绝对GAS5 < 10 ng/μl的个体患糖尿病的几率几乎高出12倍（确切优势比[OR] = 11.79 (95% CI: 3.97, 37.26), p < 0.001）。分析表明，ROC曲线下面积（AUC）为0.81，敏感性为85.1%，特异性为67.3%。阳性预测值为71.4%。lncRNA GAS5水平与T2DM患病率相关。血清中GAS5和其他参数的评估为识别糖尿病高危人群提供了更高的准确性。对参战老兵的血清样本进行了分析。分析血清lncrna水平与糖尿病的相关性。采用ROC分析确定GAS5的最佳截止值。绝对GAS5 < 10 ng/μl的个体患糖尿病的几率几乎高出12倍。我们发现GAS5 lncRNA是糖尿病的重要指标。
Diabetes mellitus (DM), a metabolic disease, is characterized by impaired fasting glucose levels. Type 2 DM is adult onset diabetes. Long non-coding RNAs (lncRNAs) regulate gene expression and multiple studies have linked lncRNAs to human diseases. Serum samples obtained from 96 participating veterans at JAH VA were deposited in the Research Biospecimen Repository. We used a two-stage strategy to identify an lncRNA whose levels correlated with T2DM. Initially we screened five serum samples from diabetic and non-diabetic individuals using lncRNA arrays. Next, GAS5 lncRNA levels were analyzed in 96 serum samples using quantitative PCR. Receiver operating characteristic (ROC) analysis was performed to determine the optimal cutoff GAS5 for diagnosis of DM. Our results demonstrate that decreased GAS5 levels in serum were associated with diabetes in a cohort of US military veterans. The ROC analysis revealed an optimal cutoff GAS5 value of less than or equal to 10. qPCR results indicated that individuals with absolute GAS5 < 10 ng/μl have almost twelve times higher odds of having diabetes (Exact Odds Ratio [OR] = 11.79 (95% CI: 3.97, 37.26), p < 0.001). Analysis indicated area under curve (AUC) of ROC of 0.81 with 85.1% sensitivity and 67.3% specificity in distinguishing non-diabetic from diabetic subjects. The positive predictive value is 71.4%. lncRNA GAS5 levels are correlated to prevalence of T2DM. Assessment of GAS5 in serum along with other parameters offers greater accuracy in identifying individuals at-risk for diabetes. Serum samples from participating veterans were analyzed. Levels of serum lncRNAs were analyzed for correlation to diabetes. ROC analysis was performed to determine GAS5 optimal cutoff. Individuals with absolute GAS5 < 10 ng/μl have almost 12 times higher odds of diabetes. We identified GAS5 lncRNA as significant indicator of diabetes.