Expression and significance of lncRNA-HOTTIP and miR-21 in serum of patients with gestational diabetes mellitus
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摘要: 目的 探究长链非编码RNA(lncRNA)-HOXA远端转录本(HOTTIP)及微小RNA-21(miR-21)在妊娠期糖尿病(GDM)患者血清中的表达及意义。方法 选取GDM孕妇89例为GDM组，选取同期正常孕妇90例为对照组，运用荧光定量PCR(RT-PCR)法检测2组血清中lncRNA-HOTTIP及miR-21表达，比较2组的差异；采用ROC曲线评估lncRNA-HOTTIP及miR-21对GDM早期诊断价值；采用Pearson相关性分析探究lncRNA-HOTTIP及miR-21与GDM临床指标关系，χ2检验检测lncRNA-HOTTIP及miR-21与妊娠不良结局关系。结果 与正常孕妇相比，GDM患者血清中lncRNA-HOTTIP及miR-21表达上调，差异有统计学意义(P< 0.05)，lncRNA-HOTTIP、miR-21及联合分析对GDM诊断曲线下面积分别为0.904、0.872、0.949；lncRNA-HOTTIP、miR-21与患者外周血生化指标及孕妇BMI呈显著相关性(P< 0.05)；lncRNA-HOTTIP、miR-21与巨大儿及总妊娠不良结局发生率相关。结论 lncRNA-HOTTIP及miR-21可以作为GDM诊断及不良妊娠结局的预测因子。
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关键词:
- 妊娠期糖尿病 /
- lncRNA-HOTTIP /
- 微小RNA-21
Abstract: Objective To explore the expression and significance of lncRNA-HOTTIP and miR-21 in serum of the patients with gestational diabetes mellitus(GDM).Methods RT-PCR was used to compare the expression of lncRNA-HOTTIP and miR-21 in the serum of GDM patients and normal pregnant women; the biochemical indexes of peripheral blood of the two groups were compared; ROC curve was used to evaluate the value of lncRNA-HOTTIP and miR-21 in early diagnosis of GDM; Pearson correlation analysis was used to explore the correlation between lncRNA-HOTTIP and miR-21 and clinical indexes of GDM, and Chi square test was used to detect the correlation between lncRNA-HOTTIP and miR-21 and adverse pregnancy outcomes.Results Compared with normal pregnant women, the expressions of lncRNA-HOTTIP and miR-21 in the serum of GDM patients were significantly up-regulated(P< 0.05). The AUC of lncRNA-HOTTIP, miR-21 and their combination analysis for early diagnosis of GDM were 0.904, 0.872 and 0.949. There was a significant correlation between lncRNA-HOTTIP and miR-21 and biochemical indexes of peripheral blood and BMI of pregnant women(P< 0.05). lncRNA-HOTTIP and miR-21 were associated with macrosomia and the incidence of adverse pregnancy outcomes.Conclusion lncRNA-HOTTIP and miR-21 can be used as predictors of GDM diagnosis and adverse pregnancy outcomes.-
Key words:
- gestational diabetes mellitus /
- lncRNA-HOTTIP /
- miR-21
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表 1 扩增引物序列
引物名称 引物序列 lncRNA HOTTIP上游引物 5’-TACGCGTATTCTTAAGCAAT-3’ lncRNA HOTTIP下游引物 5’-ACCCGTCACCGAAGAGAGTC-3’ miR-21上游引物 5’-GGGTAGCTTATCAGACTGA-3’ miR-21下游引物 5’-TGGTGTCGTGGAGTCG-3’ β-actin上游引物 5’-CGGTCAGGTCATCACTATCG-3’ β-actin下游引物 5’-CTGTGTTGGCATAGAGGTCTT-3’ U6上游引物 5’-CTCGCTTCGGGCAGCACA-3’ U6下游引物 5’-AACGCTTCACGAATTTGCGT-3’ 
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表 2 2组受试者临床检测结果
X±S 参数 对照组 GDM组 P TC/(mmol·L-1) 1.87±0.28 5.28±1.02 < 0.001 TG/(mmol·L-1) 1.31±0.16 3.59±0.71 < 0.001 HDL-C/(mmol·L-1) 4.01±0.76 1.26±0.21 < 0.001 LDL-C/(mmol·L-1) 1.23±0.19 3.18±0.61 < 0.001 FPG 4.46±0.37 7.21±0.81 < 0.001 HbA1c/% 4.28±0.91 7.01±0.78 0.012 HOMAIR 3.27±0.38 5.91±0.98 0.013
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表 3 ROC曲线评估lncRNA-HOTTIP、miR-21对GDM的诊断意义
参数 AUC 最佳临界值 敏感度/% 特异度/% Youden指数 95%CI LncRNA-HOTTIP 0.904 0.304 89.9 90.0 0.799 0.854~0.955 MiR-21 0.872 0.366 82.0 87.8 0.687 0.817~0.927 联合分析 0.949 0.269 100 87.8 0.878 0.912~0.987
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表 4 血清lncRNA-HOTTIP、miR-21表达水平与GDM临床资料相关性分析
临床参数 LncRNA-HOTTIP miR-21 r P r P 年龄 0.173 0.068 0.149 0.071 孕次 0.045 0.781 0.029 0.892 产次 0.152 0.082 0.135 0.110 BMI 18周 0.382 0.028 0.274 0.052 28周 0.404 0.011 0.441 0.009 分娩时 0.501 0.002 0.482 0.005 TC 0.621 < 0.001 0.521 < 0.001 TG 0.587 < 0.001 0.561 < 0.001 HDL-C -0.544 < 0.001 -0.537 < 0.001 LDL-C 0.509 < 0.001 0.492 0.003 FPG 0.561 < 0.001 0.521 < 0.001 HbA1c 0.628 < 0.001 0.591 < 0.001 HOMA-IR 0.601 < 0.001 0.587 < 0.001
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表 5 血清lncRNA-HOTTIP、miR-21表达与不良妊娠结局的相关性
例(%) 不良反应 LncRNA HOTTIP miR-21 高表达
(n=45)低表达
(n=44)χ2 P 高表达
(n=45)低表达
(n=44)χ2 P 羊水过多 7(15.56) 4(9.09) 0.858 0.552 5(11.63) 2(4.35) 1.625 0.202 早产 6(13.33) 3(6.82) 1.039 0.431 4(9.30) 3(6.52) 0.209 0.648 巨大儿 8(17.78) 3(6.82) 2.467 0.116 5(11.63) 3(6.52) 0.655 0.418 新生儿呼吸窘迫 4(8.89) 2(4.55) 0.751 0.398 3(6.98) 2(4.35) 0.290 0.590 合计 25(55.56) 12(27.27) 7.326 0.007 20(46.51) 10(21.74) 6.104 0.013
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