A comprehensive contribution of genetic variations of the insulin-like growth factor 1 signalling pathway to stroke susceptibility

Yao, Yingshui; Zhu, Hui; Zhu, Lijun; Fang, Zhengmei; Fan, Yao; Liu, Chunlan; Tian, Yizhu; Chen, Yan; Tang, Wei; Ren, Zeying; Li, Jie; Yang, Song; Chen, Yanchun; Zhao, Xianxian; Shen, Chong

doi:10.1016/j.atherosclerosis.2020.01.009

Cited by 4 publications

(4 citation statements)

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“…All patients had a validated diagnosis of stroke and disease status was confirmed by a neurologist according to medical records of CT or MRI. 12 Controls were randomly selected from individuals participating in a community-based survey of cardiovascular risk factors between 2013 and 2017 who were judged to be free of stroke by history, clinical examination, and self-report questionnaires.…”

Section: Methodsmentioning

confidence: 99%

“…All patients had a validated diagnosis of stroke and disease status was confirmed by a neurologist according to medical records of CT or MRI. 12 Establishment and maintenance of these cohorts have been described in detail elsewhere. 13 Briefly, the China MUCA 1998, InterASIA, and CIMIC were established in 1998, 2000-2001, and 2007-2008, respectively.…”

Section: Study Populationmentioning

confidence: 99%

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Development and Validation of a Polygenic Risk Score for Stroke in the Chinese Population

Niu

Shen

et al. 2021

Neurology

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Objective:To construct a polygenic risk score (PRS) for stroke and evaluate its utility in risk stratification and primary prevention for stroke.Methods:Using meta-analytic approach and large genome-wide association results for stroke and stroke-related traits in East Asians, we generated a combined PRS (metaPRS) by incorporating 534 genetic variants in a training set of 2,872 patients with stroke and 2,494 controls. We then validated its association with incident stroke using Cox regression models in large Chinese population-based prospective cohorts comprising 41,006 individuals.Results:During a total of 367,750 person-years (mean follow-up 9.0 years), 1,227 participants developed stroke before age of 80 years. Individuals with high polygenic risk had an about 2-fold higher risk of incident stroke compared with those with low polygenic risk (HR: 1.99, 95% CI: 1.66-2.38), with the lifetime risk of stroke being 25.2% (95% CI: 22.5%-27.7%) and 13.6% (95% CI: 11.6%-15.5%), respectively. Individuals with both high polygenic risk and family history displayed the lifetime risk as high as 41.1% (95% CI: 31.4%-49.5%). Moreover, individuals with high polygenic risk achieved greater benefits in terms of absolute risk reductions from adherence to ideal fasting blood glucose and total cholesterol than those with low polygenic risk. Maintaining favorable cardiovascular health (CVH) profile could substantially mitigate the increased risk conferred by high polygenic risk to the level of the low polygenic risk (from 34.6 % to 13.2%).Conclusions:Our metaPRS has great potential for risk stratification of stroke and identification of individuals who may benefit more from maintaining ideal CVH.Classification of Evidence:This study provides Class I evidence that a meta-polygenic risk score is predictive of stroke risk.

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Section: Methodsmentioning

confidence: 99%

Section: Study Populationmentioning

confidence: 99%

Development and Validation of a Polygenic Risk Score for Stroke in the Chinese Population

Niu

Shen

et al. 2021

Neurology

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“…There are few reports on IGFBP-1 and the risk of stroke. The results of two genetic studies have suggested that a single-nucleotide polymorphism (rs1874479) in the IGFBP1 gene is associated with increased stroke risk [21,22]. Furthermore, in a subcohort of the Cardiovascular Health Study (n = 2026), baseline fasting plasma IGFBP-1 was similar in adults aged 65 years or older that later developed stroke compared with control subjects, and IGFBP-1 did not predict the risk of stroke [23].…”

Section: Introductionmentioning

confidence: 99%

Serum IGFBP-1 Concentration as a Predictor of Outcome after Ischemic Stroke—A Prospective Observational Study

Åberg

Gadd

Jood

et al. 2023

IJMS

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Insulin-like growth factor-binding protein-1 (IGFBP-1) regulates insulin-like growth factor-I (IGF-I) bioactivity, and is a central player in normal growth, metabolism, and stroke recovery. However, the role of serum IGFBP-1 (s-IGFBP-1) after ischemic stroke is unclear. We determined whether s-IGFBP-1 is predictive of poststroke outcome. The study population comprised patients (n = 470) and controls (n = 471) from the Sahlgrenska Academy Study on Ischemic Stroke (SAHLSIS). Functional outcome was evaluated after 3 months, 2, and 7 years using the modified Rankin Scale (mRS). Survival was followed for a minimum of 7 years or until death. S-IGFBP-1 was increased after 3 months (p < 0.01), but not in the acute phase after stroke, compared with the controls. Higher acute s-IGFBP-1 was associated with poor functional outcome (mRS score > 2) after 7 years [fully adjusted odds ratio (OR) per log increase 2.9, 95% confidence interval (CI): 1.4-5.9]. Moreover, higher s-IGFBP-1 after 3 months was associated with a risk of poor functional outcome after 2 and 7 years (fully adjusted: OR 3.4, 95% CI: 1.4–8.5 and OR 5.7, 95% CI: 2.5–12.8, respectively) and with increased mortality risk (fully adjusted: HR 2.0, 95% CI: 1.1–3.7). Thus, high acute s-IGFBP-1 was only associated with poor functional outcome after 7 years, whereas s-IGFBP-1 after 3 months was an independent predictor of poor long-term functional outcome and poststroke mortality.

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“…In addition, decreased circulating levels of IGF-1 and IGFBP3 have been correlated with a greater incidence of ischemic heart and cerebrovascular stroke ( 53 , 54 ). In a recent case-control study with more than 4000 participants, it was proposed that the IGF-1 signaling pathway contributes to the risk of stroke occurrence ( 55 ). Atherosclerotic plaque stability and dimensions are partly regulated by VSMCs, whose apoptosis and structural alterations influence plaque rupture ( 56 – 58 ).…”

Section: Igf-1 Systemmentioning

confidence: 99%

New insights on the cardiovascular effects of IGF-1

et al. 2023

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IntroductionCardiovascular (CV) disorders are steadily increasing, making them the world’s most prevalent health issue. New research highlights the importance of insulin-like growth factor 1 (IGF-1) for maintaining CV healthMethodsWe searched PubMed and MEDLINE for English and non-English articles with English abstracts published between 1957 (when the first report on IGF-1 identification was published) and 2022. The top search terms were: IGF-1, cardiovascular disease, IGF-1 receptors, IGF-1 and microRNAs, therapeutic interventions with IGF-1, IGF-1 and diabetes, IGF-1 and cardiovascular disease. The search retrieved original peer-reviewed articles, which were further analyzed, focusing on the role of IGF-1 in pathophysiological conditions. We specifically focused on including the most recent findings published in the past five years.ResultsIGF-1, an anabolic growth factor, regulates cell division, proliferation, and survival. In addition to its well-known growth-promoting and metabolic effects, there is mounting evidence that IGF-1 plays a specialized role in the complex activities that underpin CV function. IGF-1 promotes cardiac development and improves cardiac output, stroke volume, contractility, and ejection fraction. Furthermore, IGF-1 mediates many growth hormones (GH) actions. IGF-1 stimulates contractility and tissue remodeling in humans to improve heart function after myocardial infarction. IGF-1 also improves the lipid profile, lowers insulin levels, increases insulin sensitivity, and promotes glucose metabolism. These findings point to the intriguing medicinal potential of IGF-1. Human studies associate low serum levels of free or total IGF-1 with an increased risk of CV and cerebrovascular illness. Extensive human trials are being conducted to investigate the therapeutic efficacy and outcomes of IGF-1-related therapy.DiscussionWe anticipate the development of novel IGF-1-related therapy with minimal side effects. This review discusses recent findings on the role of IGF-1 in the cardiovascular (CVD) system, including both normal and pathological conditions. We also discuss progress in therapeutic interventions aimed at targeting the IGF axis and provide insights into the epigenetic regulation of IGF-1 mediated by microRNAs.

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A comprehensive contribution of genetic variations of the insulin-like growth factor 1 signalling pathway to stroke susceptibility

Cited by 4 publications

References 45 publications

Development and Validation of a Polygenic Risk Score for Stroke in the Chinese Population

Development and Validation of a Polygenic Risk Score for Stroke in the Chinese Population

Serum IGFBP-1 Concentration as a Predictor of Outcome after Ischemic Stroke—A Prospective Observational Study

New insights on the cardiovascular effects of IGF-1

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