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A comprehensive contribution of genetic variations of the insulin-like growth factor 1 signalling pathway to stroke susceptibility.
- Source :
-
Atherosclerosis [Atherosclerosis] 2020 Mar; Vol. 296, pp. 59-65. Date of Electronic Publication: 2020 Jan 18. - Publication Year :
- 2020
-
Abstract
- Background and Aims: The insulin-like growth factor (IGF)-1 signalling pathway has been implicated in the pathogenesis of atherosclerosis; however, the mechanism underlying its role in stroke remains unexplained. Herein, we aimed to explore the effects of genetic polymorphisms in the IGF1 pathway on stroke in the Chinese Han population.<br />Methods: Twenty-six single-nucleotide polymorphisms (SNPs) in IGF1 pathway genes were genotyped in a case-control study consisting of 2070 stroke cases and 2243 controls. Main genetic effects and gene-gene interactive effects of the IGF1 pathway were evaluated. Weighted genetic risk scores (wGRS) were computed, and the associations between wGRS and gene expression were analysed.<br />Results: The variants at GHRH rs6032470 were significantly associated with high risk of hemorrhagic stroke (HS), and the adjusted OR (95%CI) was 1.368 (1.136-1.647). Significant additive interaction between rs6032470 and gender was detected for HS and ischemic stroke (IS). The association of rs6032470 and stroke was stronger in males than in females. Additionally, a significant gene-gene interaction of rs6032470-rs1874479 (IGFBP1) in relation to HS risk was identified (p < 0.05). IGF1 mRNA expression was significantly upregulated in IS, while it was linearly downregulated across rs6214 genotypes. In addition, IGFBP3 transcript variant 2 mRNA level was negatively correlated with wGRS (r = -0.285, p = 0.005).<br />Conclusions: Our findings indicated that the IGF1 signalling pathway genes potentiated the risk of stroke through both main effects and gene-gene interactions. The genetic effect of GHRH rs6032470 on stroke was gender dependent. The wGRS of IGF1 pathway genes may be an independent predictor of stroke risk.<br />Competing Interests: Declaration of competing interest The authors declared they do not have anything to disclose regarding conflict of interest with respect to this manuscript.<br /> (Copyright © 2020 The Authors. Published by Elsevier B.V. All rights reserved.)
- Subjects :
- Adult
Age Distribution
Aged
Case-Control Studies
China epidemiology
Diabetes Mellitus epidemiology
Dyslipidemias epidemiology
Epistasis, Genetic
Ethnicity genetics
Female
Genetic Predisposition to Disease
Growth Hormone-Releasing Hormone physiology
Humans
Hypertension epidemiology
Insulin-Like Growth Factor Binding Protein 1 genetics
Insulin-Like Growth Factor Binding Protein 1 physiology
Insulin-Like Growth Factor Binding Protein 3 genetics
Insulin-Like Growth Factor Binding Protein 3 physiology
Insulin-Like Growth Factor I physiology
Male
Middle Aged
RNA, Messenger biosynthesis
Stroke epidemiology
Transcription, Genetic
Growth Hormone-Releasing Hormone genetics
Insulin-Like Growth Factor I genetics
Polymorphism, Single Nucleotide
Signal Transduction genetics
Stroke genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1879-1484
- Volume :
- 296
- Database :
- MEDLINE
- Journal :
- Atherosclerosis
- Publication Type :
- Academic Journal
- Accession number :
- 32065979
- Full Text :
- https://doi.org/10.1016/j.atherosclerosis.2020.01.009