Genetic Variants in Antioxidant Genes Are Associated With Diisocyanate-Induced Asthma

Yücesoy, Berran; Johnson, Victor J.; Lummus, Zana L.; Kissling, Grace E.; Fluharty, Kara; Gautrin, Denyse; Malo, Jean‐Luc; Cartier, André; Boulet, Louis‐Philippe; Sastre, Joaquı́n; Quirce, Santiago; Germolec, Dori R.; Tarlo, Susan M.; Cruz, María Jesús; Muñoz, Xavier; Luster, Michael I.; Bernstein, David I.

doi:10.1093/toxsci/kfs183

Cited by 43 publications

(42 citation statements)

References 51 publications

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“…Superoxide is primarily a produced ROS and its dismutation is an important antioxidant defense mechanism in the ROS production cascade [12,13]. The distribution of the MnSOD 16Ala allele varies from 11-30% in Japanese and Chinese populations to 41-62% in Caucasians [5].…”

Section: Discussionmentioning

confidence: 99%

Gene Polymorphisms of Tumor Necrosis Factor Alpha and Antioxidant Enzymes in Bronchial Asthma

Despotović¹,

Stoimenov²,

Stanković³

et al. 2015

Adv Clin Exp Med

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Background. Bronchial asthma is an inflammatory disease resulting from a combination of genetic and environmental factors. Single nucleotide polymorphisms in the regulatory regions of cytokine and antioxidant enzyme genes may affect cytokine production and enzyme activity, and thus play a contributory role in asthma pathogenesis. Objectives. The aim of this study was to examine the association of manganese superoxide dismutase (MnSOD) Ala16Val, catalase (CAT) A-21T and tumor necrosis factor alpha (TNF-α) G-308A polymorphisms with bronchial asthma. Material and Methods. A total of 79 patients with asthma and 95 healthy controls were screened for MnSOD Ala16Val, CAT A-21T and TNF-α G-308A polymorphisms using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method.

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Section: Discussionmentioning

confidence: 99%

Gene Polymorphisms of Tumor Necrosis Factor Alpha and Antioxidant Enzymes in Bronchial Asthma

Despotović¹,

Stoimenov²,

Stanković³

et al. 2015

Adv Clin Exp Med

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“…There has also been reported an association between specific HLA alleles and respiratory sensitisation to acid anhydrides (Jones et al, 2004). In addition, there has been found associations between antioxidant genes and HLA alleles with diisocyanate-induced occupational asthma (Yucesoy et al, 2012(Yucesoy et al, , 2014. The influence of genetic polymorphisms on susceptibility to developing chemical respiratory allergy has implications for the development and interpretation of relevant exposure thresholds.…”

Section: Risk Factorsmentioning

confidence: 99%

Thresholds in chemical respiratory sensitisation

et al. 2015

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There is a continuing interest in determining whether it is possible to identify thresholds for chemical allergy. Here allergic sensitisation of the respiratory tract by chemicals is considered in this context. This is an important occupational health problem, being associated with rhinitis and asthma, and in addition provides toxicologists and risk assessors with a number of challenges. In common with all forms of allergic disease chemical respiratory allergy develops in two phases. In the first (induction) phase exposure to a chemical allergen (by an appropriate route of exposure) causes immunological priming and sensitisation of the respiratory tract. The second (elicitation) phase is triggered if a sensitised subject is exposed subsequently to the same chemical allergen via inhalation. A secondary immune response will be provoked in the respiratory tract resulting in inflammation and the signs and symptoms of a respiratory hypersensitivity reaction. In this article attention has focused on the identification of threshold values during the acquisition of sensitisation. Current mechanistic understanding of allergy is such that it can be assumed that the development of sensitisation (and also the elicitation of an allergic reaction) is a threshold phenomenon; there will be levels of exposure below which sensitisation will not be acquired. That is, all immune responses, including allergic sensitisation, have threshold requirement for the availability of antigen/allergen, below which a response will fail to develop. The issue addressed here is whether there are methods available or clinical/epidemiological data that permit the identification of such thresholds. This document reviews briefly relevant human studies of occupational asthma, and experimental models that have been developed (or are being developed) for the identification and characterisation of chemical respiratory allergens. The main conclusion drawn is that although there is evidence that the acquisition of sensitisation to chemical respiratory allergens is a dose-related phenomenon, and that thresholds exist, it is frequently difficult to define accurate numerical values for threshold exposure levels. Nevertheless, based on occupational exposure data it may sometimes be possible to derive levels of exposure in the workplace, which are safe. An additional observation is the lack currently of suitable experimental methods for both routine hazard characterisation and the measurement of thresholds, and that such methods are still some way off. Given the current trajectory of toxicology, and the move towards the use of non-animal in vitro and/or in silico) methods, there is a need to consider the development of alternative approaches for the identification and characterisation of respiratory sensitisation hazards, and for risk assessment.

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“…Genetic variations in genes coding for enzymatic antioxidants, glutathione S-transferases (GSTs), manganese superoxide dismutase (SOD2), and microsomal epoxide hydrolase are also associated with increased susceptibility to diisocyanate-induced occupational asthma [33]. These antioxidants are considered to be protective against oxidative stress, which may be caused by diisocyanates.…”

Section: Geneticsmentioning

confidence: 99%