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

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

doi:10.1016/j.gene.2025.149226

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

Gene. 2025 Jan 9:149226. doi: 10.1016/j.gene.2025.149226. Online ahead of print.

Authors

Runqiu Yang¹, Xin Wang¹, Yi Zhang¹, Lei Jin², Kai Zhao³, Juan Chen⁴, Xuejun Shang⁵, Yuanzhong Zhou⁶, Hongsong Yu⁷

Affiliations

¹ Department of Immunology, Special Key Laboratory of Gene Detection and Therapy of Guizhou Province, Zunyi Medical University, Zunyi, China.
² Institute of Reproductive and Child Health, National Health Commission Key Laboratory of Reproductive Health, Peking University, Beijing, China.
³ Institute of Reproductive Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
⁴ Department of Occupational and Environmental Health, School of Public Health, Xi'an Jiaotong University Health Science Center, Xi'an, China.
⁵ Department of Urology, Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China.
⁶ School of Public Health,Key Laboratory of Maternal & Child Health and Exposure Science of Guizhou Higher Education Institutes, Zunyi Medical University, Zunyi, China. Electronic address: [email protected].
⁷ Department of Immunology, Special Key Laboratory of Gene Detection and Therapy of Guizhou Province, Zunyi Medical University, Zunyi, China. Electronic address: [email protected].

PMID: 39798826
DOI: 10.1016/j.gene.2025.149226

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 O₃ 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; O₃: P = 0.013, OR = 1.002; PM_2.5: P = 0.042, OR = 1.005；BC: P = 0.048, OR = 1.094; NO₃^-:P = 0.045, OR = 1.024).

Conclusion: GDM is significantly associated with IGF2BP2/rs11927381 and CAPN10/rs2975760 polymorphisms as well as exposure to O₃. Furthermore, the interaction between the CAPN10/rs2975760 CC genotype and IGF2BP2/rs11927381 TC genotype, as well as environmental factors (O₃, PM_2.5, BMI), significantly increases the risk of GDM in Chinese women.

Keywords: CAPN10; GDM; Gene-environment interactions; IGF2BP2; O(3); PM(2.5).