Ozone exposure, vitamin C intake, and genetic susceptibility of asthmatic children in Mexico City: a cohort study

Abstract

BackgroundWe previously reported that asthmatic children with GSTM1 null genotype may be more susceptible to the acute effect of ozone on the small airways and might benefit from antioxidant supplementation. This study aims to assess the acute effect of ozone on lung function (FEF25-75) in asthmatic children according to dietary intake of vitamin C and the number of putative risk alleles in three antioxidant genes: GSTM1, GSTP1 (rs1695), and NQO1 (rs1800566).Methods257 asthmatic children from two cohort studies conducted in Mexico City were included. Stratified linear mixed models with random intercepts and random slopes on ozone were used. Potential confounding by ethnicity was assessed. Analyses were conducted under single gene and genotype score approaches.ResultsThe change in FEF25-75 per interquartile range (60 ppb) of ozone in persistent asthmatic children with low vitamin C intake and GSTM1 null was −91.2 ml/s (p = 0.06). Persistent asthmatic children with 4 to 6 risk alleles and low vitamin C intake showed an average decrement in FEF25-75 of 97.2 ml/s per 60 ppb of ozone (p = 0.03). In contrast in children with 1 to 3 risk alleles, acute effects of ozone on FEF25-75 did not differ by vitamin C intake.ConclusionsOur results provide further evidence that asthmatic children predicted to have compromised antioxidant defense by virtue of genetic susceptibility combined with deficient antioxidant intake may be at increased risk of adverse effects of ozone on pulmonary function.

Modification of the Effect of Ambient Air Pollution on Pediatric Asthma Emergency Visits

“…Further evidence supporting effect modification by race comes from two controlled ozone-exposure studies in which African American men exhibited greater decrements in lung function following exposure than either white men or African American women. 33,34 Although the mechanisms underlying these observed differences have not been fully elaborated, several genetic factors have been investigated, 35 and some factors reported to affect susceptibility to ozone (such as micronutrient deficiencies 36 and elevated body mass index) 37 may be more prevalent in African American populations. Further research is needed to clarify how race may affect susceptibility.…”

Asthma in Latin America

“…[35][36][37][38] Two studies replicated interactions between candidate genes (IL10 and TGFB1) and dust mite allergen in Costa Ricans in an independent cohort, and another demonstrated that violence exposure is associated with DNA methylation of the gene for the pituitary adenylate cyclase-activating polypeptide type 1 receptor (ADCYAP1R1), which is in turn associated with asthma in Puerto Rican children.…”

“…A study in Mexico City showed that children with low vitamin C levels and certain GSTM1 genotypes may be more susceptible to the negative effects of ozone exposure on lung function. 37 These findings suggest that low levels of antioxidants such as vitamin D or C may lead to increased oxidative stress or, alternatively, more severe viral infections after exposure to pollutants.…”

Mechanisms of carbon nanotube‐induced pulmonary fibrosis: a physicochemical characteristic perspective

“…Activation and dimerization of STAT1 leads to translocation of the dimerized transcription factors and expression of genes that are involved in growth inhibition. Individuals with idiopathic fibrosis and systemic sclerosis have decreased STAT1 transcription and expression as well as fibroblast hyper-proliferation and apoptotic resistance 111 . STAT1 knockout mice exhibit an increased susceptibility to bleomycin induced fibrosis 112 .…”