洪琳凤 李桦 郭晴虹 肖鸽飞 金丰梅 尹保民 张超敏 严津晶 蔡鹏飞 李兆生

【摘要】 目的：分析細胞周期激酶抑制因子4基因座中反义非编码RNA（ANRIL）表达水平与妊娠期糖尿病（GDM）的相关性。方法：选择2019年7月-2020年6月于本院产科进行产检并分娩的妊娠期妇女122例，根据孕24～28周口服葡萄糖耐量试验（OGTT）结果是否异常将其分为OGTT异常组（n=61）和OGTT正常组（n=61）。比较两组血清激素[雌二醇（E2）、孕酮（P）]水平以及lncRNA ANRIL表达水平，分析lncRNA ANRIL表达水平与GDM患者激素水平的相关性。结果：两组孕期体重增加、FPG、餐后1 h血糖、餐后2 h血糖比较，差异均有统计学意义（P<0.05）。OGTT异常组血清E2、P水平均显著高于OGTT正常组，差异均有统计学意义（P<0.05）。OGTT异常组血清lncRNA ANRIL mRNA表达水平显著高于OGTT正常组，差异有统计学意义（P<0.05）。Pearson相关分析显示，血清lncRNA ANRIL mRNA表达与GDM患者E2、P水平均呈明显正相关（P<0.05）。logistic回归模型分析结果显示，lncRNA ANRIL是影响GDM发生的危险因素（P<0.001）。结论：GDM患者lncRNA ANRIL表达水平显著升高，并与激素水平呈显著正相关，lncRNA ANRIL表达升高可能是机体抵抗胰岛功能的影响因素。

【关键词】 妊娠期糖尿病 细胞周期激酶抑制因子4基因座中反义非编码RNA 雌二醇 孕酮 相关性

Correlation between ANRIL expression level and gestational diabetes mellitus/HONG Linfeng， LI Hua， GUO Qinghong， XIAO Gefei， JIN Fengmei， YIN Baomin， ZHANG Chaomin， YAN Jinjing， CAI Pengfei， LI Zhaosheng. //Medical Innovation of China， 2021， 18（05）： -146

[Abstract] Objective： To analyze the correlation between expression level of antisense non-coding RNA in the INK4 locus （ANRIL） and gestational diabetes mellitus （GDM）. Method： A total of 122 pregnant women who underwent obstetric examination and delivery in our hospital from July 2019 to June 2020 were selected. According to the abnormal results of oral glucose tolerance test （OGTT） at 24 to 28 weeks of pregnancy， they were divided into abnormal OGTT group （n=61） and normal OGTT group （n=61）. The levels of serum hormones [estradiol （E2）， progesterone （P）]and expression level of lncRNA ANRIL were compared between the two groups. The correlation between expression level of lncRNA-ANRIL and hormones levels were analyzed among GDM patients. Result： There were statistically significant differences in weight gain， FPG， 1 h postprandial blood glucose and 2 h postprandial blood glucose during pregnancy （P<0.05）. Serum E2 and P levels in the abnormal OGTT group were significantly higher than those in the normal OGTT group， with statistical significance （P<0.05）. The expression level of lncRNA ANRIL mRNA in serum of OGTT abnormal group was significantly higher than that of OGTT normal group， with statistical significance （P<0.05）. Pearson correlation analysis showed that serum lncRNA ANRIL mRNA expression was significantly positively correlated with E2 and P levels in GDM patients （P<0.05）. Logistic regression model showed that lncRNA ANRIL was a risk factor for the occurrence of GDM （P<0.001）. Conclusion： The expression level of lncRNA ANRIL in patients with GDM is significantly increased， and is significantly positively correlated with the levels of hormones. The increase of lncRNA ANRIL expression may be an influencing factor for the bodys islet resistance function.

[Key words] Gestational diabetes mellitus Antisense non-coding RNA in the INK4 locus Estradiol Progesterone Correlation

First-authors address： Zhuhai Maternal and Child Health Care Hospital， Zhuhai 519000， China

doi：10.3969/j.issn.1674-4985.2021.05.036

妊娠期糖尿病（gestational diabetes mellitus， GDM）是高危妊娠的重要原因之一[1]。早診断、早治疗对改善妊娠期糖尿病患者临床结局有着极其重要的意义。长链非编码RNA（long non-coding RNA， lncRNA）是指一类无开放阅读框的含有200个核苷酸的RNA，lncRNA参与了包括糖尿病在内的各种疾病的病理过程[2]。细胞周期激酶抑制因子4基因座中反义非编码RNA（antisense non-coding RNA in the INK4 locus， ANRIL）又被称为lncRNA ANRIL，是最早发现的lncRNA之一[3]。全基因组关联研究表明，lncRNA ANRIL是2型糖尿病（type 2 diabetes mellitus， T2DM）的遗传易感位点[4]，染色体9p21区域糖尿病相关危险变异子与ANRIL表达的下调相关。目前研究认为，lncRNA ANRIL可能是通过调节INK4b-ARF-INK4a基因[5-6]，并通过多种机制参与2型糖尿病的发病过程。但其是否与GDM发病有关，目前未见相关报道。据此，本文通过研究ANRIL表达水平与妊娠期糖尿病的相关性，旨在为妊娠期糖尿病的早诊断、早治疗提供新的参考根据，现报道如下。

1 资料与方法