U-shaped association between serum IGF2BP3 and T2DM: A cross-sectional study in Chinese population 血清IGF2BP3与2型糖尿病的U型关联:一项中国人群横断面研究

IF 3 2区 医学 Q2 ENDOCRINOLOGY & METABOLISM
Xiaoying Wu, Wei Wang, Shujin Fan, Lili You, Feng Li, Xiaoyun Zhang, Hongshi Wu, Juying Tang, Yiqin Qi, Wanting Feng, Li Yan, Meng Ren
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引用次数: 3

摘要

目的探讨n6 -甲基腺苷(m6A)调节因子在2型糖尿病(T2DM)发病中的表达。我们进一步探讨了高危人群血清胰岛素样生长因子2 mrna结合蛋白3 (IGF2BP3)水平与T2DM发病几率的关系。方法从gene expression Omnibus中获取基因表达数据集GSE25724,利用R软件包ComplexHeatmap生成聚类热图。采用非配对t检验对13个m6A RNA甲基化调控因子在非糖尿病对照组和T2DM受试者之间的差异表达进行分析。横断面设计包括393名受试者(131名新诊断的T2DM患者,131名年龄和性别匹配的前驱糖尿病患者,131名健康对照)。血清IGF2BP3浓度与T2DM之间的关系通过限制三次样条和logistic回归模型建模。结果T2DM患者胰岛样本中发现2个m6a相关基因表达上调(IGF2BP2和IGF2BP3), 5个m6a相关基因表达下调(甲基转移酶样3 [METTL3]、烷基化修复同源蛋白1 [ALKBH1]、YTH结构域家族2 [YTHDF2]、YTHDF3和异质核核糖核蛋白[HNRNPC])。根据三次自然样条分析模型,在调整体重指数、腰围、舒张压、总胆固醇和甘油三酯后,血清IGF2BP3水平与T2DM发病率呈u型相关。多因素logistic回归显示,模型4中血清IGF2BP3水平低于0.62 ng/mL时,T2DM的发病几率逐渐增加(优势比3.03[95%可信区间1.23-7.47])。结论T2DM患者存在7个m6A RNA甲基化基因显著改变。在中国普通成年人中,血清IGF2BP3水平与2型糖尿病发病率呈u型相关。本研究为进一步研究m6A RNA甲基化,特别是血清IGF2BP3在T2DM风险评估中的作用提供了重要证据。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
U-shaped association between serum IGF2BP3 and T2DM: A cross-sectional study in Chinese population 血清IGF2BP3与2型糖尿病的U型关联:一项中国人群横断面研究

Objective

To clarify the expression of N6-methyladenosine (m6A) modulators involved in the pathogenesis of type 2 diabetes mellitus (T2DM). We further explored the association of serum insulin-like growth factor 2 mRNA-binding proteins 3 (IGF2BP3) levels and odds of T2DM in a high-risk population.

Methods

The gene expression data set GSE25724 was obtained from the Gene Expression Omnibus, and a cluster heatmap was generated by using the R package ComplexHeatmap. Differential expression analysis for 13 m6A RNA methylation regulators between nondiabetic controls and T2DM subjects was performed using an unpaired t test. A cross-sectional design, including 393 subjects (131 patients with newly diagnosed T2DM, 131 age- and sex-matched subjects with prediabetes, and 131 healthy controls), was carried out. The associations between serum IGF2BP3 concentrations and T2DM were modeled by restricted cubic spline and logistic regression models.

Results

Two upregulated (IGF2BP2 and IGF2BP3) and 5 downregulated (methyltransferase-like 3 [METTL3], alkylation repair homolog protein 1 [ALKBH1], YTH domain family 2 [YTHDF2], YTHDF3, and heterogeneous nuclear ribonucleoprotein [HNRNPC]) m6A-related genes were found in islet samples of T2DM patients. A U-shaped association existed between serum IGF2BP3 levels and odds of T2DM according to cubic natural spline analysis models, after adjustment for body mass index, waist circumference, diastolic blood pressure, total cholesterol, and triglyeride. Multivariate logistic regression showed that progressively higher odds of T2DM were observed when serum IGF2BP3 levels were below 0.62 ng/mL (odds ratio 3.03 [95% confidence interval 1.23–7.47]) in model 4.

Conclusion

Seven significantly altered m6A RNA methylation genes were identified in T2DM. There was a U-shaped association between serum IGF2BP3 levels and odds of T2DM in the general Chinese adult population. This study provides important evidence for further examination of the role of m6A RNA methylation, especially serum IGF2BP3 in T2DM risk assessment.

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来源期刊
Journal of Diabetes
Journal of Diabetes ENDOCRINOLOGY & METABOLISM-
CiteScore
6.50
自引率
2.20%
发文量
94
审稿时长
>12 weeks
期刊介绍: Journal of Diabetes (JDB) devotes itself to diabetes research, therapeutics, and education. It aims to involve researchers and practitioners in a dialogue between East and West via all aspects of epidemiology, etiology, pathogenesis, management, complications and prevention of diabetes, including the molecular, biochemical, and physiological aspects of diabetes. The Editorial team is international with a unique mix of Asian and Western participation. The Editors welcome submissions in form of original research articles, images, novel case reports and correspondence, and will solicit reviews, point-counterpoint, commentaries, editorials, news highlights, and educational content.
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