Insulin-like growth factor-I gene polymorphism and risk of heart failure (the Rotterdam Study)

Erasmus MC, Rotterdam, South Holland, Netherlands
The American Journal of Cardiology (Impact Factor: 3.28). 09/2004; 94(3):384-6. DOI: 10.1016/j.amjcard.2004.04.044
Source: PubMed


We studied 4,963 participants of the population-based Rotterdam Study and found that a genetically determined chronic exposure to low insulin-like growth factor-I (IGF-I) levels is associated with an increased risk for heart failure in elderly patients.

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    • "In recent years, low levels of IGF-1 have been suggested to increase the risk of developing cardiovascular disease particularly myocardial infarction.12,13 Moreover, data analyses based on Framingham and Rotterdam studies have reported low levels of IGF-1 to be associated with the risk of developing heart failure.14,15 Further studies have emphasized the stimulating effect of insulin like growth factors on left ventricular remodeling and long term survival following myocardial infarction.11,13,16,17 "
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    ABSTRACT: In recent years, low levels of Insulin-like Growth Factor-1 (IGF-1) have been suggested to be associated with higher risks of developing heart failure and higher long-term mortality rates following Acute Myocardial Infarction (AMI). However, the effect of IGF-1 levels on short-term survival has been rarely studied. In this study we aimed to assess any possible association between serum IGF-1 concentration following AMI and short-term survival rates. In this study, serum total IGF-1 levels were measured in 56 patients within 24 hours following AMI and were compared to 56 individuals with no cardiovascular disease. Patients were followed up to death or discharge from hospital (median = 6 days) and survival curves were compared based on median IGF-1 value. Mean (±SD) of serum IGF-1 levels were 232.73 ng/ml (±81.74) and 211.00 ng/ml (±58.22) in survived and expired patients respectively and the difference was not statistically significant (P value = 0.501). The difference between survival curves was also not statistically significant (P value = 0.246). According to findings of this study, serum total IGF-1 concentration does not seem to be associated with short-term survival rates.
    Clinical Medicine Insights: Cardiology 02/2011; 5:7-11. DOI:10.4137/CMC.S6629
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    • "Several evidences have indicated that IGF- I plays a crucial role in protection of cardiomyocytes and low IGF-I levels are associated with high risk for myocardial infarction and heart failure [6] [7]. Two major IGF-I signaling pathways, including Ras-Raf-1-Mek-ERK and 3-kinase (PI 3- kinase)-Akt pathways, have been linked to cardiac growth, proliferation, and anti-apoptotic responses [8] [9] [10] [11]. Both Fas-dependent and mitochondrial-dependent apoptotic pathways are considered as major pathways "
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    ABSTRACT: Apoptosis involves in the pathogenesis of various cardiac abnormalities. This study intends to evaluate the effects of Li-Fu formula on cardiac apoptosis induced by hyper-cholesterol diet. Twenty-four male Golden Syrian hamsters were randomly divided into Control, Cholesterol and Li-Fu formula groups. Histopathological analysis, western blotting and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assays were performed to measure the effects of Li-Fu formula on left ventricle. Significantly reduced TUNEL-positive cells and mitochondria- dependent apoptosis were observed in the left ventricle of hamsters from Li-Fu formula group compared to the Cholesterol group. Additionally, induced cardiac insulin like growth factor I receptor (IGFIR)-dependent survival pathway was detected in the Li-Fu formula group compared to the Cholesterol group. Besides, minor fibrosis, increased collagen deposition, and myofibril disarray was detected in the Cholesterol group, whereas the reductions of collagen deposition and myofibril disarray were observed in the Li-Fu formula group. This study demonstrated that Li-Fu formula not only reduced the mitochondria-dependent apoptosis and fibrosis, but also enhanced the IGF-I survival pathway in the left ventricle from high cholesterol-fed hamsters. We suggest the protective effects of Li-Fu formula on cardiac apoptosis and therapeutic potentials against cardiovascular disease.
    Evidence-based Complementary and Alternative Medicine 11/2009; 2011(1741-427X):530345. DOI:10.1093/ecam/nep182 · 1.88 Impact Factor
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    ABSTRACT: A polymorphism near the promoter region of the IGF-I gene has been associated with serum IGF-I levels, body height and birth weight. In this study, we investigated whether this polymorphism is associated with body composition in young healthy subjects in two cohorts of different generations. Observational study with repeated measurements. The study group consisted of two comparable young Dutch cohorts with a generational difference of around 20 years. The older cohort consisted of 359 subjects born between 1961 and 1965. Measurements were performed from 13 until 36 years of age. The younger cohort consisted of 258 subjects born between 1981 and 1989. Measurements were performed from 8 until 14 years of age. Height, body mass index (BMI), fat mass, fat-free mass, waist and hip circumference were compared between wild-type carriers and variant type carriers of the IGF-I polymorphism. In the younger cohort, body weight, BMI, fat mass and waist circumference were significantly higher in female variant carriers of the IGF-I polymorphism. A similar trend was observed in male variant carriers. In contrast, these differences were not observed in the older cohort. Irrespective of genotype, the younger cohort showed a significantly higher total fat mass, body weight and BMI compared with the older cohort. Because the differences between both genotypes were small, it seems likely that the genetic variability due to this IGF-I polymorphism impacts only slightly on body composition. Importantly, our study suggested that associations between this IGF-I promoter polymorphism and body composition possibly reflect a gene-environmental interaction of this polymorphism and that an environment that promotes obesity leads to a slightly more pronounced fat accumulation in variant carriers of this IGF-I polymorphism.
    European Journal of Endocrinology 04/2006; 154(3):379-88. DOI:10.1530/eje.1.02101 · 4.07 Impact Factor
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