Association of ORMDL3, STAT6 and TBXA2R gene polymorphisms with asthma

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

doi:10.1111/j.1744-313x.2011.01051.x

Cited by 23 publications

(12 citation statements)

References 31 publications

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“…No significant association with the disease risk was detected for STAT6-21C/T, similar to the analysis in [73] but contrary to other studies [19, 40–44]. However, STAT6-21*TT is overrepresented in asthmatics with a ≥10 mm wheal size reaction to storage mites and shows a significant epistatic interaction with IL4-590C/T between moderate-severe persistent and intermittent asthma.…”

Section: Discussionsupporting

confidence: 64%

Genetic polymorphisms and asthma: findings from a case–control study in the Madeira island population

Berenguer¹,

Fernandes²,

Oliveira³

et al. 2014

Biol Res

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BackgroundAsthma is a complex disease influenced by multiple genetic and environmental factors. While Madeira has the highest prevalence of asthma in Portugal (14.6%), the effect of both genetic and environmental factors in this population has never been assessed. We categorized 98 asthma patients according to the Global Initiative for Asthma (GINA) guidelines, established their sensitization profile, and measured their forced expiratory volume in 1 second (FEV1) and forced vital capacity (FVC) indexes. Selected single nucleotide polymorphisms (SNPs) were analysed as potential markers for asthma susceptibility and severity in the interleukin 4 (IL4), interleukin 13 (IL13), beta-2-adrenergic receptor (ADRB2), a disintegrin and metalloprotease 33 (ADAM33), gasdermin-like (GSDML) and the signal transducer and activator of transcription 6 (STAT6) genes comparatively to a population reference set.ResultsAlthough mites are the major source of allergic sensitization, no significant difference was found amongst asthma severity categories. IL4-590*CT/TT and IL4-RP2*253183/183183 were found to predict the risk (2-fold) and severity (3 to 4-fold) of asthma and were associated with a lower FEV1 index. ADRB2-c.16*AG is a risk factor (3.5-fold), while genotype GSDML-236*TT was protective (4-fold) for moderate-severe asthma. ADAM33-V4*C was associated to asthma and mild asthma by the transmission disequilibrium test (TDT). Finally, ADAM33-V4*CC and STAT6-21*TT were associated with higher sensitization (mean wheal size ≥10 mm) to house dust (1.4-fold) and storage mite (7.8-fold).ConclusionIn Madeira, IL4-590C/T, IL4-RP2 253/183, GSDML-236C/T and ADAM33-V4C/G SNPs are important risk factors for asthma susceptibility and severity, with implications for asthma healthcare management.Electronic supplementary materialThe online version of this article (doi:10.1186/0717-6287-47-40) contains supplementary material, which is available to authorized users.

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Section: Discussionsupporting

confidence: 64%

Genetic polymorphisms and asthma: findings from a case–control study in the Madeira island population

Berenguer¹,

Fernandes²,

Oliveira³

et al. 2014

Biol Res

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“…Firstly, in vitro study of the ORMDL3 promoter revealed that Est-1, p300, and CREB are regulators of ORMDL3 expression and that the levels of these regulators correlated with expression of ORMDL3 in recurrent wheeze patients (43). Later, STAT6 was shown to be a direct regulator of ORMDL3 expression (44), confirming previous findings that both ORMDL3 and STAT6 are associated with asthma (45). Furthermore, the role of chromatin in ORMDL3 expression was evaluated.…”

Section: Association Of Ormdl3 With Asthma and Other Pathologiessupporting

confidence: 65%

The role of ORMDL proteins, guardians of cellular sphingolipids, in asthma

Paulenda

Dráber

2016

Allergy

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To cite this article: Paulenda T, Draber P. The role of ORMDL proteins, guardians of cellular sphingolipids, in asthma. AbstractA family of widely expressed ORM-like (ORMDL) proteins has been recently linked to asthma in genomewide association studies in humans and extensively explored in in vivo studies in mice. ORMDL proteins are key regulators of serine palmitoyltransferase, an enzyme catalyzing the initial step of sphingolipid biosynthesis. Sphingolipids play prominent roles in cell signaling and response to stress, and they affect the mechanistic properties of cellular membranes. Deregulation of sphingolipid biosynthesis and their recycling has been proven to support and even cause several diseases including allergy, inflammation, and asthma. ORMDL3, the most extensively studied member of the ORMDL family, has been shown to be important for endoplasmic reticulum homeostasis by regulating the unfolded protein response and calcium response. In immune cells, ORMDL3 is involved in migration and in the production of proinflammatory cytokines. Furthermore, changes in the expression level of ORMDL3 are important in allergen-induced asthma pathologies. This review focuses on functional aspects of the ORMDL family proteins, which may serve as new therapeutic targets for the treatment of asthma and some other life-threatening diseases.

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“…In addition, STAT6 gene polymorphisms are associated with asthma-related symptoms but not with the risk of developing asthma (Begh é et al, 2010;Kavalar et al, 2012).…”

Section: Stats In the Pathogenesis Of Bronchial Asthmamentioning

confidence: 99%

Role of Transcription Factors in the Pathogenesis of Asthma and COPD

Caramori¹,

Casolari²,

Adcock

2013

Cell Communication & Adhesion

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Infl ammation is a central feature of asthma and chronic obstructive pulmonary disease (COPD). Despite recent advances in the knowledge of the pathogenesis of asthma and COPD, much more research on the molecular mechanisms of asthma and COPD are needed to aid the logical development of new therapies for these common and important diseases, particularly in COPD where no effective treatments currently exist. In the future the role of the activation/repression of different transcription factors and the genetic regulation of their expression in asthma and COPD may be an increasingly important aspect of research, as this may be one of the critical mechanisms regulating the expression of different clinical phenotypes and their responsiveness to therapy, particularly to anti-infl ammatory drugs.

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Association of ORMDL3, STAT6 and TBXA2R gene polymorphisms with asthma

Cited by 23 publications

References 31 publications

Genetic polymorphisms and asthma: findings from a case–control study in the Madeira island population

Genetic polymorphisms and asthma: findings from a case–control study in the Madeira island population

The role of ORMDL proteins, guardians of cellular sphingolipids, in asthma

Role of Transcription Factors in the Pathogenesis of Asthma and COPD

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