Insulin-like growth factor 2 (IGF2 ) and IGF-binding protein 1 (IGFBP1) gene variants are associated with overfeeding-induced metabolic changes

Ukkola, Olavi; Sun, Guang; Bouchard, Claude

doi:10.1007/s001250100034

Cited by 44 publications

(39 citation statements)

References 13 publications

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“…Our results are in conflict with a previous study (Ukkola et al, 2001), which found that carriers of the less frequent G variant allele of SNP rs3793344, located in a region of intron 1 of IGFBP1, which harbours sequences affecting gene expression, had significantly lower circulating levels of IGF-I both before and after overfeeding. Subjects carrying two copies of the A allele had lower IGF-I concentrations before overfeeding, which were further decreased after overfeeding compared to subjects carrying the rarer G allele.…”

Section: Discussioncontrasting

confidence: 99%

“…We found no evidence of higher IGF-I concentrations with this polymorphism. It is possible that the previously reported association (Ukkola et al, 2001) is linked to the peculiar study conditions (long-term caloric surplus). Alternatively, the association could be due to a statistical fluctuation caused by the small sample size of the study (12 pairs of monozygotic twins).…”

Section: Discussionmentioning

confidence: 95%

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Polymorphisms of genes coding for insulin-like growth factor 1 and its major binding proteins, circulating levels of IGF-I and IGFBP-3 and breast cancer risk: results from the EPIC study

et al. 2006

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Insulin-like growth factor I (IGF-I) stimulates cell proliferation and can enhance the development of tumours in different organs. Epidemiological studies have shown that an elevated level of circulating IGF-I is associated with increased risk of breast cancer, as well as of other cancers. Most of circulating IGF-I is bound to an acid-labile subunit and to one of six insulin-like growth factor binding proteins (IGFBPs), among which the most important are IGFBP-3 and IGFBP-1. Polymorphisms of the IGF1 gene and of genes encoding for the major IGF-I carriers may predict circulating levels of IGF-I and have an impact on cancer risk. We tested this hypothesis with a case -control study of 807 breast cancer patients and 1588 matched control subjects, nested within the European Prospective Investigation into Cancer and Nutrition. We genotyped 23 common single nucleotide polymorphisms in IGF1, IGFBP1, IGFBP3 and IGFALS, and measured serum levels of IGF-I and IGFBP-3 in samples of cases and controls. We found a weak but significant association of polymorphisms at the 5 0 end of the IGF1 gene with breast cancer risk, particularly among women younger than 55 years, and a strong association of polymorphisms located in the 5 0 end of IGFBP3 with circulating levels of IGFBP-3, which confirms previous findings. Common genetic variation in these candidate genes does not play a major role in altering breast cancer risk in Caucasians.

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Section: Discussioncontrasting

confidence: 99%

Section: Discussionmentioning

confidence: 95%

Polymorphisms of genes coding for insulin-like growth factor 1 and its major binding proteins, circulating levels of IGF-I and IGFBP-3 and breast cancer risk: results from the EPIC study

et al. 2006

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“…sweets) might associate with ADHD symptoms in children who follow an early onset (≤ age 10; n=83) vs low (n=81) trajectory of CP, via DNA methylation of the insulin-like growth factor 2 (IGF2) gene. We focused on IGF2 due to its relevance in metabolic function [9], placental and fetal growth [10], and the development of brain regions implicated in ADHD [11][12][13]. Data was drawn from the Accessible Resource for Integrated Epigenomics Studies (ARIES) [14], a subsample of the Avon Longitudinal Study of Parents and Children (ALSPAC), which includes (a) maternal reports of diet (32 weeks gestation, age 3 and 7); (b) peripheral measures of DNA methylation (Illumina 450k) at birth and age 7 (n=671, 49% male) and (c) repeated assessments of psychiatric symptomatology, including CP (ages 4-13) and ADHD (ages 7-13).…”

Section: Introductionmentioning

confidence: 99%

Prenatal Diet and Childhood ADHD: Exploring the Potential Role of IGF2 Methylation

2016

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“…However, conflicting results have been reported for both gene variants (15-17). Preliminary results, based on oral glucose tolerance test (OGTT) data, have suggested a ␤-cell defect in carriers of gene variants in both genes (13,14; N. Vaessen, personal communication).In this study, we analyzed glucose-stimulated insulin secretion in relation to the presence of the (CA) n repeat polymorphism in the IGF-I gene and the ApaI polymorphism in the IGF-II gene (10,13). As described previously, all participants underwent a hyperglycemic clamp at 10 mmol/l glucose to assess insulin secretion (18 -20).…”

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confidence: 99%

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confidence: 99%

Genetic Factors and Insulin Secretion

et al. 2004

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IGFs are important regulators of pancreatic ␤-cell development, growth, and maintenance. Mutations in the IGF genes have been found to be associated with type 2 diabetes, myocardial infarction, birth weight, and obesity. These associations could result from changes in insulin secretion. We have analyzed glucose-stimulated insulin secretion using hyperglycemic clamps in carriers of a CA repeat in the IGF-I promoter and an ApaI polymorphism in the IGF-II gene. Normal and impaired glucose-tolerant subjects (n ‫؍‬ 237) were independently recruited from three different populations in the Netherlands and Germany to allow independent replication of associations. Both first-and second-phase insulin secretion were not significantly different between the various IGF-I or IGF-II genotypes. Remarkably, noncarriers of the IGF-I CA repeat allele had both a reduced insulin sensitivity index (ISI) and disposition index (DI), suggesting an altered balance between insulin secretion and insulin action. IGFs are regulators of processes like growth and metabolism (1-3). IGF-I and IGF-II also contribute to pancreatic ␤-cell growth and development by regulating ␤-cell replication, renewal, and apoptosis (4,5). Deregulation of the balance between ␤-cell renewal and apoptosis due to alterations in IGF levels is potentially of great importance in the development of glucose intolerance. In addition, insulin-dependent glucose homeostasis may be affected by IGFs by sharing common steps in the signaling pathways of receptors for IGFs and insulin (6). Defects in the IGF/insulin-signaling pathways affect fetal growth and thus birth weight, which is a known risk factor for type 2 diabetes and other parts of the metabolic syndrome during life (7). Furthermore, it has been shown in animal models that ablation of the IGF-I receptor from pancreatic ␤-cells results in the absence of the first phase of glucose-stimulated insulin secretion and a strong reduction in second-phase insulin secretion (8,9). Together, these data make it plausible that defects at the level of IGF-I or IGF-II are associated with alterations in glucosestimulated insulin secretion resulting in glucose intolerance.Previously, it was shown that polymorphisms in the IGF-I and IGF-II genes are associated with features of the metabolic syndrome (10 -13). A (CA) n repeat in the promoter region of the IGF-I gene associates with type 2 diabetes, cardiovascular disease, and reduced birth weight (10,14). Gene variants in the IGF-II gene are found in association studies with BMI and IGF-II levels (11,12). However, conflicting results have been reported for both gene variants (15-17). Preliminary results, based on oral glucose tolerance test (OGTT) data, have suggested a ␤-cell defect in carriers of gene variants in both genes (13,14; N. Vaessen, personal communication).In this study, we analyzed glucose-stimulated insulin secretion in relation to the presence of the (CA) n repeat polymorphism in the IGF-I gene and the ApaI polymorphism in the IGF-II gene (10,13). As described previously,...

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Insulin-like growth factor 2 (IGF2 ) and IGF-binding protein 1 (IGFBP1) gene variants are associated with overfeeding-induced metabolic changes

Cited by 44 publications

References 13 publications

Polymorphisms of genes coding for insulin-like growth factor 1 and its major binding proteins, circulating levels of IGF-I and IGFBP-3 and breast cancer risk: results from the EPIC study

Polymorphisms of genes coding for insulin-like growth factor 1 and its major binding proteins, circulating levels of IGF-I and IGFBP-3 and breast cancer risk: results from the EPIC study

Prenatal Diet and Childhood ADHD: Exploring the Potential Role of IGF2 Methylation

Genetic Factors and Insulin Secretion

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