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ORIGINAL RESEARCH article

Front. Mol. Neurosci.
Sec. Molecular Signalling and Pathways
Volume 17 - 2024 | doi: 10.3389/fnmol.2024.1394994

IGF2 confers genetic susceptibility to the risk of ischemic stroke with differential mRNA expression in leukocytes

Provisionally accepted
Haining Xie Haining Xie 1Changying Chen Changying Chen 2Xu Han Xu Han 2Jing Wang Jing Wang 3*Lai Wei Lai Wei 2Zhanyun Ren Zhanyun Ren 4*Jie Li Jie Li 4*Shiyuan Gu Shiyuan Gu 4Nan Wu Nan Wu 3*Mengxue Du Mengxue Du 3*Su Hai Fei Su Hai Fei 3Yan Chen Yan Chen 3Yuelong Jin Yuelong Jin 3*Lijun Zhu Lijun Zhu 3*Zhengmei Fang Zhengmei Fang 3*Yingshui Yao Yingshui Yao 3*Chong Shen Chong Shen 2*
  • 1 School of Medical Information, Wannan Medical College, Wuhu, Anhui Province, China
  • 2 Nanjing Medical University, Nanjing, Jiangsu Province, China
  • 3 School of Public Health, Wannan Medical College, Wuhu, Anhui Province, China
  • 4 Yixing People's Hospital, Yixing, Jiangsu, China

The final, formatted version of the article will be published soon.

    Background Insulin-like growth factor 2 (IGF2), has been proven to be involved in metabolic regulation, vascular health, neuroprotection, and inflammation modulation which are relevant to the mechanism of ischemic stroke (IS). This study aimed to investigate the effect of IGF2 variants and mRNA expression on IS. Methods Three tag SNPs rs3741211, rs10770125, rs2585 were genotyped in a case-control study consisting of 2497 IS patients and 3135 controls, and two cohorts (4080 stroke-free individuals and 2298 IS patients) to evaluate the genetic effect on the incidence and prognosis of IS. IGF2 mRNA expression in leukocytes was measured in 318 IS patients and 315 controls. Results In the case-control study, the variations of rs3741211 (A>G) and rs2585 (G>A) were significantly associated with the increased risk of IS and odds ratios (ORs) of dominant model were 1.130 and 1.151 with P values of 0.024 and 0.017, respectively. The association of rs3741211 and IS remains significant in hypertension group (adjusted OR: 1.268; P=0.003) with additive interactions of hypertension (P<0.05). IGF2 mRNA expression level of IS cases were significantly lower than controls (fold change = 0.740, P = 0.002) and there was a nonlinear relationship between IGF2 mRNA expression level of IS (P<0.05). Furthermore, the variations of rs3741211, rs10770125, and rs2585 are significantly associated with increased expression levels of IGF2 mRNA (P<0.05).Additionally, a negative correlation was observed between IGF2 mRNA level and both National Institutes of Health Stroke Scale (NIHSS) and Modified Rankin Scale (mRS) scores in IS patients after discharge (P<0.05). Conclusion The study reveals that IGF2 gene contributes tois associated with the susceptibility ofto IS and rs3741211, rs10770125, and rs2585 may affect the expression levels of IGF2 mRNA. Furthermore, IGF2 mRNA level was downregulated in IS patients and negatively correlate with poor prognosis.

    Keywords: Insulin-like Growth Factor 2, ischemic stroke, Single nucleotide polymorphism, mRNA expression, case-control study, cohort study

    Received: 02 Mar 2024; Accepted: 28 Jun 2024.

    Copyright: © 2024 Xie, Chen, Han, Wang, Wei, Ren, Li, Gu, Wu, Du, Fei, Chen, Jin, Zhu, Fang, Yao and Shen. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence:
    Jing Wang, School of Public Health, Wannan Medical College, Wuhu, Anhui Province, China
    Zhanyun Ren, Yixing People's Hospital, Yixing, 214200, Jiangsu, China
    Jie Li, Yixing People's Hospital, Yixing, 214200, Jiangsu, China
    Nan Wu, School of Public Health, Wannan Medical College, Wuhu, Anhui Province, China
    Mengxue Du, School of Public Health, Wannan Medical College, Wuhu, Anhui Province, China
    Yuelong Jin, School of Public Health, Wannan Medical College, Wuhu, Anhui Province, China
    Lijun Zhu, School of Public Health, Wannan Medical College, Wuhu, Anhui Province, China
    Zhengmei Fang, School of Public Health, Wannan Medical College, Wuhu, Anhui Province, China
    Yingshui Yao, School of Public Health, Wannan Medical College, Wuhu, Anhui Province, China
    Chong Shen, Nanjing Medical University, Nanjing, 210029, Jiangsu Province, China

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