VEGFA variants are associated with pre-school lung function, but not neonatal lung function

Kreiner‐Møller, Eskil; Chawes, Bo; Vissing, Nadja Hawwa; Koppelman, Gerard H.; Postma, Dirkje S.; Madsen, Jonna Skov; Olsen, Dorte Aalund; Baty, Florent; Vonk, Judith M.; Kerkhof, Marjan; Sleiman, Patrick; Hakonarsson, Hakon; Mortensen, Li Juel; Poorisrisak, Porntiva; Bisgaard, Hans; Bønnelykke, Klaus

doi:10.1111/cea.12188

Cited by 17 publications

(14 citation statements)

References 38 publications

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“…22 A study in preschool kids found that rs6900017 of VEGFA gene was associated with their lung function at school age, but not at birth that suggested a potential function of VEGFA variants in lung development. 23 Although no studies of the function of rs879825 and rs9369421 so far, they are in high linkage disequilibrium with rs6900017 as we found in our study. VEGFA also has been identified as the primary tumor angiogenesis factor and targeted by several newly developed agents for patients with metastatic carcinoma.…”

Section: Discussioncontrasting

confidence: 52%

Carboplatin/taxane-induced gastrointestinal toxicity: a pharmacogenomics study on the SCOTROC1 trial

Winham

Hoskins

et al. 2015

Pharmacogenomics J

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Carboplatin/taxane combination is first-line therapy for ovarian cancer. However, patients can encounter treatment delays, impaired quality of life, even death because of chemotherapy-induced gastrointestinal (GI) toxicity. A candidate gene study was conducted to assess potential association of genetic variants with GI toxicity in 808 patients who received carboplatin/taxane in the Scottish Randomized Trial in Ovarian Cancer 1 (SCOTROC1). Patients were randomized into discovery and validation cohorts consisting of 404 patients each. Clinical covariates and genetic variants associated with grade III/IV GI toxicity in discovery cohort were evaluated in replication cohort. Chemotherapy-induced GI toxicity was significantly associated with seven single-nucleotide polymorphisms in the ATP7B, GSR, VEGFA and SCN10A genes. Patients with risk genotypes were at 1.53 to 18.01 higher odds to develop carboplatin/taxane-induced GI toxicity (P<0.01). Variants in the VEGF gene were marginally associated with survival time. Our data provide potential targets for modulation/inhibition of GI toxicity in ovarian cancer patients.

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Section: Discussioncontrasting

confidence: 52%

Carboplatin/taxane-induced gastrointestinal toxicity: a pharmacogenomics study on the SCOTROC1 trial

Winham

Hoskins

et al. 2015

Pharmacogenomics J

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“…In the promoter region of the VEGF gene, we found no significant difference between the asthma and control groups, although rs699947 has been reported to be associated with VEGF plasma level, pre-school lung function, and lung cancer risk (Kreiner-Møller et al, 2013;Fan et al, 2015), and the G allele of rs2010963 has been reported to be associated with asthma (Lachheb et al, 2008). These differences probably result from disparities in the sample sizes, populations, and clinical phenotypes.…”

Section: Discussioncontrasting

confidence: 51%

Polymorphisms in the vascular endothelial growth factor (VEGF) gene associated with asthma

Lu¹,

Zhao²,

Fu³

2016

Genet. Mol. Res.

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ABSTRACT. It has been proven that vascular endothelial growth factor (VEGF) is involved in airway restoration and the development of asthma. We sought to examine the relevance of VEGF gene polymorphisms to asthma in the Chinese Han population. We extracted the whole genomic DNA from the peripheral blood of 471 participants, including 226 patients with asthma and 245 healthy controls. Seven single nucleotide polymorphisms (SNPs) of the VEGF gene were genotyped using the MassARRAY system. The data were then analyzed using HaploView 4.0 and SPSS 20.0 softwares. When comparing the asthma and control groups, significant differences were found in the genotype frequencies of rs3025020 and rs3025039 (P = 0.001 and P = 0.011, respectively). The T alleles in rs3025020 and rs3025039 were significantly more prevalent in the asthma group than in controls (P = 0.0003, P = 0.001, respectively). Furthermore, a strong linkage 2 H.Y. Lu et al.

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“…Though the exact role of TET1 in such cascade is yet to be elucidated, it is evident that DEP exposure upregulates proinflammatory cytokines in airway epithelial cells with well-established roles in asthma (61-67). Therefore, it is plausible that DEP-associated oxidative stress and inflammation in airways regulate TET1 , which in turn modulates the 5-hmC levels, resulting in transcriptional activation of downstream genes such as VEGFA, which is known to be associated with lung function (68), particulate matter exposure and asthma (69-71). Interestingly, our study showed methylation of TET1 promoter may be a mechanism for regulation of TET1 .…”

Section: Discussionmentioning

confidence: 99%

Ten-eleven translocation 1 (TET1) methylation is associated with childhood asthma and traffic-related air pollution

Somineni

Zhang

Myers

et al. 2016

Journal of Allergy and Clinical Immunology

111

110

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Background Asthma is a complex disorder influenced by genetics and the environment. Recent findings have linked abnormal DNA methylation in T cells with asthma; however, the potential dysregulation of methylation in airway epithelial cells is unknown. Studies of mouse models of asthma have observed greater levels of 5-hydoxymethylcytosine (5-hmC) and TET1 expression in lungs. TET proteins are known to catalyze methylation through modification of 5-mC to 5-hydroxymethylcytosine (5-hmC). Objective Associations between TET1 methylation and asthma and traffic-related air pollution were examined. Methods TET1 methylation levels from DNA derived from nasal airway epithelial cells collected from 12 African-American children with physician-diagnosed asthma and their non-asthmatic siblings were measured using Illumina 450K arrays. Regions of interest were verified by locus-specific pyrosequencing in 35 additional sibling pairs and replicated in an independent population (N=186). Exposure to traffic-related air pollution (TRAP) at participants’ early life and current home addresses was estimated using a land-use regression model. Methylation studies in saliva, PBMCs, and human bronchial epithelial cells (HBEC) were done to support our findings. Results Loss of methylation at a single CpG site in the TET1 promoter (cg23602092) and increased global 5hmC was significantly associated with asthma. In contrast, TRAP exposure at participants’ current homes significantly increased methylation at the same site. Patterns were consistent across tissue sample types. 5-aza-2'-deoxycytidine and diesel exhaust particle exposure in HBEC was associated with altered TET1 methylation, expression and global 5-hmC. Conclusions Our findings suggest a possible role of TET1 methylation in asthma and response to TRAP. Capsule summary TET1 DNA methylation might serve as a biomarker for asthma and higher risk of exposure-related asthma exacerbations.

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VEGFA variants are associated with pre-school lung function, but not neonatal lung function

Abstract: VEGF gene variants are associated with lung function at school age, but not at birth, suggesting a role of VEGF in post-natal lung function development.

Cited by 17 publications

References 38 publications

Carboplatin/taxane-induced gastrointestinal toxicity: a pharmacogenomics study on the SCOTROC1 trial

Carboplatin/taxane-induced gastrointestinal toxicity: a pharmacogenomics study on the SCOTROC1 trial

Polymorphisms in the vascular endothelial growth factor (VEGF) gene associated with asthma

Ten-eleven translocation 1 (TET1) methylation is associated with childhood asthma and traffic-related air pollution

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