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

Abstract

Background: We 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 (FEF(25-75)) 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).

Methods: 257 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.

Results: The change in FEF(25-75) 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 FEF(25-75) 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.

Conclusions: Our 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.

Figure 1

Study design. In the antioxidant study, asthmatic children were recruited from 1998 to 2000 and followed during 12 weeks with spirometric tests during the follow-up. At baseline, children were randomly assigned to either a placebo or a supplementation group (vitamin C 250 mg/day and vitamin E 50 mg/day). In the EVA study, asthmatic children were recruited and followed during 16 weeks from 2003 to 2004. Every two weeks children had a spirometric test. In both studies, children provided blood sample at baseline.

Figure 2

Effect of ozone on FEF_25-75 and 95% CI according to genotypes and vitamin C intake. Persistently asthmatic children with vitamin C intake between 30 to 105 mg/day and with GSTM1 null had lower levels of FEF_25-75 than children with either GSTM1 positive genotype or dietary vitamin C intake higher than 105 mg/day. Similar situation was observed for Val/Val vs. Ile/Val + Ile/Ile GSTP1 polymorphisms. Linear mixed models were adjusted for age, gender, BMI, height, cohort, time, use of bronchodilator, and previous day’s minimum temperature. Reported values correspond to the effect on FEF_25-75 per 60 ppb of ozone.

Figure 3

Effect of ozone on FEF_25-75 and 95% CI according to genotype score and vitamin C intake. Persistently asthmatic children with vitamin C intake between 30 to 105 mg/day (low diet) and with 4 to 6 risk alleles had lower levels of FEF_25-75 than children with either 1 to 3 risk alleles or dietary vitamin C intake higher than 105 mg/day (high diet). Linear mixed models were adjusted for age, gender, BMI, height, cohort, time, use of bronchodilator, and previous day’s minimum temperature. N = 137 asthmatic children and 2715 repeated measures.