Asthma Treatment Outcome in Children Is Associated with Vascular Endothelial Growth Factor A (VEGFA) Polymorphisms

Balantic, M.; Rijavec, Matija; Kavalar, Maja Skerbinjek; Šuškovič, Stanislav; Šilar, Mira; Košnik, Mitja; Korošec, Peter

doi:10.1007/bf03262206

Cited by 25 publications

(21 citation statements)

References 31 publications

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“…Single nucleotide polymorphisms (SNPs) are increasingly studied as possible markers for predicting patient's treatment response [6]. In asthma, several genes have been associated with treatment response, like TBX21, VEGFA, CRHR1 and others [7,8,9]. Recently, genome-wide association study (GWAS) found rs37973 in a promoter region of glucocorticoid-induced transcript 1 (GLCCI1) to be a major candidate associated with asthma treatment response to ICS and the results were further replicated in additional cohort [10].…”

Section: Introductionmentioning

confidence: 99%

GLCCI1 Polymorphism rs37973 and Response to Treatment of Asthma With Inhaled Corticosteroids

Rijavec¹,

Žavbi²,

Lopert³

et al. 2018

J Investig Allergol Clin Immunol

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Background. Asthma treatment response is highly variable and pharmacogenetic markers that predict treatment response would be one step closer to personalized treatment. GWAS studies have shown that polymorphisms GLCCI1 could be associated with asthma treatment response to inhaled corticosteroids (ICS).Materials and methods. We genotyped rs37973 of GLCCI1 in 208 adult asthma patients treated with ICS. Change in % predicted FEV1 was analysed after short-term (3 months) and after long-term (at least 3 years) treatment. Treatment success was defined as good when FEV1 decreased less than 30 ml/year.Results. After 3 months of treatment, change of % predicted FEV1 was higher in patients with GG genotype than in patients with AG+AA genotype, and this genotype dependent difference was only evident in non-smokers. Similar results were found after at least 3 years of treatment when all patients were analysed, in non-smokers and patients with atopy. Even though, no differences in treatment success (good vs. poor response) were observed when analysing the entire group of patients, genotype dependent treatment success was highly influenced by smoking and atopy. GG genotype was overrepresented in non-smokers and patients with atopy with good response.Conclusions. Rs37973 was associated with short-and long-term treatment response; however, there was a great influence of smoking and atopy on pharmacogenetic association. Furthermore, we found GG genotype to be associated with better treatment response, what is contrary to results found in GWAS.Keywords: pharmacogenetics, rs37973, GLCCI1, FEV1, smoking, atopy ResumenIntroducción: La respuesta al tratamiento del asma es muy variable y los marcadores farmacogenéticos que predicen esta respuesta nos sitúan más cerca del tratamiento personalizado. Los estudios de asociación de genoma completo (GWAS) han demostrado que los polimorfismos GLCCI1 podrían estar asociados con la respuesta al tratamiento con corticosteroides inhalados (ICS).Material y métodos. Se genotipó el polimorfismo de un solo nucleótico (SNP) rs37973 de GLCCI1 en 208 pacientes adultos con asma tratados con ICS. El cambio en el porcentual de lFEV1 predicho se analizó después de un tratamiento a corto plazo (3 meses) y después de un tratamiento a largo plazo (al menos 3 años). El éxito del tratamiento se definió como bueno cuando el FEV1 disminuyó menos de 30 ml / año.Resultados. Después de 3 meses de tratamiento, el cambio en el porcentual del FEV1 predicho fue mayor en pacientes con genotipo GG que en pacientes con genotipo AG + AA, y esta diferencia asociada al genotipo solo fue evidente en los no fumadores. Se encontraron resultados similares, en el análisis de la muestra completa de pacientes, después de al menos 3 años de tratamiento, tanto en no fumadores y como en pacientes atópicos. A pesar de que no se observaron diferencias en el éxito del tratamiento (buena frente a mala respuesta) al analizar todo el grupo de pacientes, el éxito del tratamiento dependiente del genotipo estuvo muy influenciado por el...

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Section: Introductionmentioning

confidence: 99%

GLCCI1 Polymorphism rs37973 and Response to Treatment of Asthma With Inhaled Corticosteroids

Rijavec¹,

Žavbi²,

Lopert³

et al. 2018

J Investig Allergol Clin Immunol

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“…VEGF also enhances antigen sensitization and T H 2-mediated inflammation in the lung [4]. Furthermore, VEGF-A polymorphisms are associated with asthma treatment outcome and lung function [9,10] and blocking VEGF seems a potential treatment for asthma [2,11]. Therefore, the regulatory mechanism of VEGF expression in the airway deserves further study.…”

Section: Introductionmentioning

confidence: 99%

Aryl hydrocarbon receptor agonists upregulate VEGF secretion from bronchial epithelial cells

et al. 2015

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“…Of these studies, 33 met the inclusion criteria (Fig. ), with 29 being candidate gene studies (Table S3) and four being GWAS .…”

Section: Methodsmentioning

confidence: 99%

“…Only four SNPs within three genes (CRHR1: rs242941, rs1876828; GLCCI1:rs37973 and FCER2: rs28364072) were positively replicated at least once ( Table 2). Response to medication was assessed using different outcomes: lung function measurements such as changes in FEV1 over time [16][17][18][19][20][21][22][23][24][25][26][27][28][29], annual decline ). in FEV1 [30][31][32], bronchial hyperresponsiveness [BHR] to methacholine [26,29,33,34], asthma symptoms based on questionnaires [25,[35][36][37][38][39][40] and exacerbations despite treatment [37,38,[41][42][43].…”

Section: Candidate Gene Studies Of Icsmentioning

confidence: 99%

Pharmacogenomics of inhaled corticosteroids and leukotriene modifiers: a systematic review

Farzan

Vijverberg

Arets

et al. 2016

Clin Experimental Allergy

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Asthma Treatment Outcome in Children Is Associated with Vascular Endothelial Growth Factor A (VEGFA) Polymorphisms

Cited by 25 publications

References 31 publications

GLCCI1 Polymorphism rs37973 and Response to Treatment of Asthma With Inhaled Corticosteroids

GLCCI1 Polymorphism rs37973 and Response to Treatment of Asthma With Inhaled Corticosteroids

Aryl hydrocarbon receptor agonists upregulate VEGF secretion from bronchial epithelial cells

Pharmacogenomics of inhaled corticosteroids and leukotriene modifiers: a systematic review

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