胰岛素样生长因子2 mRNA结合蛋白2（IGF2BP2）和钙蛋白酶10（CAPN10）的基因变异及其与环境因素的相互作用增加了中国女性患妊娠期糖尿病的风险。

Genetic variations in IGF2BP2 and CAPN10 and their interaction with environmental factors increase gestational diabetes mellitus risk in Chinese women.

作者信息

Yang Runqiu, Wang Xin, Zhang Yi, Jin Lei, Zhao Kai, Chen Juan, Shang Xuejun, Zhou Yuanzhong, Yu Hongsong

机构信息

Department of Immunology, Special Key Laboratory of Gene Detection and Therapy of Guizhou Province, Zunyi Medical University, Zunyi, China.

Institute of Reproductive and Child Health, National Health Commission Key Laboratory of Reproductive Health, Peking University, Beijing, China.

出版信息

Gene. 2025 Mar 15;941:149226. doi: 10.1016/j.gene.2025.149226. Epub 2025 Jan 9.

DOI:10.1016/j.gene.2025.149226

PMID:39798826

Abstract

AIM

This study aims to investigate the association of the genetic variations in IGF2BP2 and CAPN10 as well as gene-environment interactions with the risk of gestational diabetes (GDM) in Chinese women.

MATERIALS AND METHODS

A total of 1,566 pregnant Chinese women participated in this case-control study. We employed targeted next-generation sequencing to analyze specific SNPs in IGF2BP2 (rs11927381, rs1470579, rs4402960, rs7640539) and CAPN10/rs2975760. Various genetic models were used to assess the associations of these polymorphisms with GDM risk. Gene-gene and gene-environment interactions were examined using GMDR to identify interaction models, Subsequently, logistic regression was employed to confirm the significance of these models and to evaluate their impact on GDM susceptibility.

RESULTS

Our study identified significant associations between the C allele of IGF2BP2/rs11927381 and an increased GDM susceptibility in both dominant (P = 0.031, OR = 1.247) and heterozygote (P = 0.043, OR = 1.239) gene models. Conversely, the heterozygote TC genotype of CAPN10/rs2975760 was associated with a reduced risk of GDM (P = 0.046, OR = 0.766). Increased BMI and O levels were linked to a higher GDM susceptibility. We discovered interactions between CAPN10/rs2975760 CC and IGF2BP2/rs11927381 TC genotype that exacerbated GDM risk (P = 0.022, OR = 11.337). Furthermore, interactions between IGF2BP2/rs11927381 and environmental factors were observed, indicating increased GDM risks (BMI: P = 0.004, OR = 1.011; O: P = 0.013, OR = 1.002; PM: P = 0.042, OR = 1.005；BC: P = 0.048, OR = 1.094; NO:P = 0.045, OR = 1.024).

CONCLUSION

GDM is significantly associated with IGF2BP2/rs11927381 and CAPN10/rs2975760 polymorphisms as well as exposure to O. Furthermore, the interaction between the CAPN10/rs2975760 CC genotype and IGF2BP2/rs11927381 TC genotype, as well as environmental factors (O, PM, BMI), significantly increases the risk of GDM in Chinese women.

摘要

目的

本研究旨在探讨中国女性中胰岛素样生长因子2 mRNA结合蛋白2（IGF2BP2）和钙蛋白酶10（CAPN10）的基因变异以及基因-环境相互作用与妊娠期糖尿病（GDM）风险的关联。

材料与方法

共有1566名中国孕妇参与了这项病例对照研究。我们采用靶向二代测序技术分析IGF2BP2（rs11927381、rs1470579、rs4402960、rs7640539）和CAPN10/rs2975760中的特定单核苷酸多态性（SNP）。使用多种遗传模型评估这些多态性与GDM风险的关联。采用基因多因素降维法（GMDR）检测基因-基因和基因-环境相互作用以确定相互作用模型，随后采用逻辑回归来确认这些模型的显著性并评估它们对GDM易感性的影响。

结果

我们的研究发现，在显性（P = 0.031，比值比[OR]=1.247）和杂合子（P = 0.043，OR = 1.239）基因模型中，IGF2BP2/rs11927381的C等位基因与GDM易感性增加显著相关。相反，CAPN10/rs2975760的杂合子TC基因型与GDM风险降低相关（P = 0.046，OR = 0.766）。体重指数（BMI）升高和空腹血糖（O）水平升高与GDM易感性增加有关。我们发现CAPN10/rs2975760的CC基因型与IGF2BP2/rs11927381的TC基因型之间存在相互作用，加剧了GDM风险（P = 0.022，OR = 11.337）。此外，还观察到IGF2BP2/rs11927381与环境因素之间的相互作用，表明GDM风险增加（BMI：P = 0.004，OR = 1.011；O：P = 0.013，OR = 1.002；餐后血糖[PM]：P = 0.042，OR = 1.005；空腹血糖[BC]：P = 0.048，OR = 1.094；一氧化氮[NO]：P = 0.045，OR = 1.024）。