A polymorphism at IGF1 locus is associated with carotid intima media thickness and endothelium-dependent vasodilatation

Sesti, Giorgio; Mannino, Gaia Chiara; Andreozzi, Francesco; Greco, Annalisa; Perticone, Maria; Sciacqua, Angela; Marini, Maria Adelaide; Perticone, Francesco

doi:10.1016/j.atherosclerosis.2013.10.024

Cited by 23 publications

(30 citation statements)

References 44 publications

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“…In fact, Chen et al (2013) recently demonstrated that the IGF1 rs35767 SNP together with two neighbour SNPs constitutes a haplotype that efficiently regulates transcriptional activity (Chen et al 2013). Similarly, several studies have consistently reported that carriers of the IGF1 rs35767T allele showed significantly higher levels of circulating IGF1 than those harbouring the WT allele (Mannino et al 2013, Sesti et al 2014 and that the presence of this variant is associated with an increased risk of developing several types of cancer (Ollberding et al 2012, Qian et al 2014.…”

Section: Endocrine-related Cancermentioning

confidence: 99%

Type 2 diabetes-related variants influence the risk of developing multiple myeloma: results from the IMMEnSE consortium

Lupiañez¹,

Campa²,

Martino³

et al. 2015

Endocrine-Related Cancer

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Type 2 diabetes (T2D) has been suggested to be a risk factor for multiple myeloma (MM), but the relationship between the two traits is still not well understood. The aims of this study were to evaluate whether 58 genome-wide-association-studies (GWAS)-identified common variants for T2D influence the risk of developing MM and to determine whether predictive models built with these variants might help to predict the disease risk. We conducted a case-control study including 1420 MM patients and 1858 controls ascertained through the International Multiple Myeloma (IMMEnSE) consortium. Subjects carrying the KCNQ1 rs2237892T allele or the CDKN2A-2B rs2383208G/G , IGF1 rs35767T/T and MADD rs7944584T/T genotypes had a significantly increased risk of MM (odds ratio (OR)Z1.32-2.13) whereas those carrying the KCNJ11 rs5215C , KCNJ11 rs5219T and THADA rs7578597C alleles or the FTO rs8050136A/A and LTA rs1041981C/C genotypes showed a significantly decreased risk of developing the disease (ORZ0.76-0.85). Interestingly, a prediction model including those T2D-related variants associated with the risk of MM showed a significantly improved discriminatory ability to predict the disease when compared to a model without genetic information (area under the curve (AUC)Z0.645 vs AUCZ0.629; PZ4.05! 10 K06). A gender-stratified analysis also revealed a significant gender effect modification for ADAM30 rs2641348 and NOTCH2 rs10923931 variants (P interaction Z0.001 and 0.0004, respectively). Men carrying the ADAM30 rs2641348C and NOTCH2 rs10923931T alleles had a significantly decreased risk of MM whereas an opposite but not significant effect was observed in women (OR M Z0.71 and OR M Z0.66 vs OR W Z1.22 and OR W Z1.15, respectively). These results suggest that TD2-related variants may influence the risk of developing MM and their genotyping might help to improve MM risk prediction models.

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Section: Endocrine-related Cancermentioning

confidence: 99%

Type 2 diabetes-related variants influence the risk of developing multiple myeloma: results from the IMMEnSE consortium

Lupiañez¹,

Campa²,

Martino³

et al. 2015

Endocrine-Related Cancer

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“…IGF-1 level has been inversely linked with atherosclerosis [30], and rs35767 polymorphisms in the IGF1 gene are associated with IGF-1 serum level [31]. Previously, we studied the relationship between IGF1 gene polymorphisms and in-stent restenosis in patients undergoing bare metal stent implantation, but we did not find any association [32].…”

Section: Discussionmentioning

confidence: 84%

“…Previously, we studied the relationship between IGF1 gene polymorphisms and in-stent restenosis in patients undergoing bare metal stent implantation, but we did not find any association [32]. In contrast to polymorphisms in FGF2 and EGF , polymorphism rs35767 in the IGF1 gene was studied in the context of atherosclerosis; however, data are scarce [31]. Sesti G. et al showed that rs35767 was associated with not only IGF-1 level but also intima-media thickness [31].…”

Section: Discussionmentioning

confidence: 99%

“…In contrast to polymorphisms in FGF2 and EGF , polymorphism rs35767 in the IGF1 gene was studied in the context of atherosclerosis; however, data are scarce [31]. Sesti G. et al showed that rs35767 was associated with not only IGF-1 level but also intima-media thickness [31]. Another paper analyzed the association between polymorphisms in the IGF1 gene and coronary arteriosclerosis.…”

Section: Discussionmentioning

confidence: 99%

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The association of functional polymorphisms in genes encoding growth factors for endothelial cells and smooth muscle cells with the severity of coronary artery disease

Osadnik

Strzelczyk

Lekston

et al. 2016

BMC Cardiovasc Disord

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BackgroundDespite the important roles of vascular smooth muscle cells and endothelial cells in atherosclerotic lesion formation, data regarding the associations of functional polymorphisms in the genes encoding growth factors with the severity of coronary artery disease (CAD) are lacking. The aim of the present study is to analyze the relationships between functional polymorphisms in genes encoding basic fibroblast growth factor (bFGF, FGF2), epidermal growth factor (EGF), insulin-like growth factor-1 (IGF-1), platelet derived growth factor-B (PDGFB), transforming growth factor-β1 (TGF-β1) and vascular endothelial growth factor A (VEGF-A) and the severity of coronary atherosclerosis in patients with stable CAD undergoing their first coronary angiography.MethodsIn total, 319 patients with stable CAD who underwent their first coronary angiography at the Silesian Centre for Heart Diseases in Zabrze, Poland were included in the analysis. CAD burden was assessed using the Gensini score. The TaqMan method was used for genotyping of selected functional polymorphisms in the FGF2, PDGFB, TGFB1, IGF1 and VEGFA genes, while rs4444903 in the EGF gene was genotyped using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. The associations between the selected polymorphisms and the Gensini were calculated both for the whole cohort and for a subgroup of patients without previous myocardial infarction (MI).ResultsThere were no differences in the distribution of the Gensini score between the genotypes of the analyzed polymorphisms in FGF2, EGF, IGF1, PDFGB, and TGFB1 in the whole cohort and in the subgroup of patients without previous MI. The Gensini score for VEGFA rs699947 single-nucleotide polymorphism (SNP) in patients without previous myocardial infarction, after correction for multiple testing, was highest in patients with the A/A genotype, lower in heterozygotes and lowest in patients with the C/C genotype, (p value for trend = 0.013, false discovery rate (FDR) = 0.02). After adjustment for clinical variables, and correction for multiple comparisons the association between the VEGFA genotype and Gensini score remained only nominally significant (p = 0.04, FDR = 0.19) under the dominant genetic model in patients without previous MI.ConclusionsWe were unable to find strong association between analyzed polymorphisms in growth factors and the severity of coronary artery disease, although there was a trend toward association between rs699947 and the severity of CAD in patients without previous MI.Electronic supplementary materialThe online version of this article (doi:10.1186/s12872-016-0402-4) contains supplementary material, which is available to authorized users.

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“…Thus, the association between IGF-1 genotype and anemia can give an unconfounded test of whether IGF-1 levels causally influence outcomes. In an attempt to clarify this issue, we took advantage of the opportunity to study the association of an IGF-1-raising polymorphism near IGF1 (rs35767) [23–28]. Indeed, it has been repeatedly reported that carriers of the rs35767 T allele exhibit higher levels of circulating IGF-1 [23–28].…”

Section: Introductionmentioning

confidence: 99%

A polymorphism at IGF1 locus is associated with anemia

et al. 2017

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In vitro and in vivo studies suggest that IGF-1 has a role in erythropoiesis. There is evidence that the rs35767 C/T polymorphism near IGF1 is associated with plasma IGF-1 levels. We investigated the effect of this polymorphism on hemoglobin (Hb) concentration and anemia. The study group comprised 3286 adult Whites. The rs35767 polymorphism was screened using a TaqMan allelic discrimination assay. The rs35767 polymorphism was not associated with age, gender, BMI, waist circumference, smoking, blood pressure, plasma glucose, HbA1c, type 2 diabetes, HOMA-IR, hsCRP, eGFR, and lipid profile. Erythrocyte sedimentation rate (ESR), fibrinogen, and fasting insulin levels were significantly lower in TT genotype carriers compared with C allele carriers. Hb concentration was significantly higher in carriers of the TT genotype compared with C allele carriers, and a lower proportion of TT carriers had anemia. As compared with TT genotype carriers, those bearing the CC genotype had a 2.4-fold higher risk of anemia (OR 2.40, 95%CI 1.19-4.82), and those with the CT genotype had a 2.0-fold higher risk of anemia (OR 2.06, 95%CI 1.04-4.11). The association remained significant when fasting insulin, eGFR, smoking, diabetes, ACE inhibitors, sartans or diuretics treatments, use of metformin and pioglitazone were added to the model, but its independence was not retained after inclusion of fibrinogen and ESR values into the model. In conclusion, rs35767 TT allele carriers exhibited significantly higher concentrations of Hb, and lower risk of anemia compared with C allele carriers supporting the idea that IGF-1 plays a role in erythropoiesis homeostasis.

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A polymorphism at IGF1 locus is associated with carotid intima media thickness and endothelium-dependent vasodilatation

Cited by 23 publications

References 44 publications

Type 2 diabetes-related variants influence the risk of developing multiple myeloma: results from the IMMEnSE consortium

Type 2 diabetes-related variants influence the risk of developing multiple myeloma: results from the IMMEnSE consortium

The association of functional polymorphisms in genes encoding growth factors for endothelial cells and smooth muscle cells with the severity of coronary artery disease

A polymorphism at IGF1 locus is associated with anemia

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