Candidate gene expression in response to low-level air pollution.

BACKGROUND

Epidemiological studies have linked air pollutant to adverse health effects even at low exposure levels, but limited evidence is available on its associations with gene expression levels.

AIM

To investigate associations between air pollutants and gene expression levels.

METHODS

We collected data from Brisbane System Genetics Study (BSGS) - a family-based system genetics study. Expression levels of candidate genes were obtained for whole blood from 266 pairs of twins (192 monozygotic and 74 dizygotic pairs) and 165 parents. Data on individual phenotypes were also obtained, including age, sex, Body Mass Index and exposure to smoke. Daily data on mean temperature and air pollutants, including particulate matter with aerodynamic diameter ≤2.5 μm (PM), ozone (O), nitrogen dioxide (NO) and sulfur dioxide (SO), were collected from seven monitoring stations for the day when the blood samples were collected. The association between each air pollutant and expression level of each gene was analyzed by using generalized linear models with adjustment for temperature and individual phenotypes, and its difference between monozygotic and dizygotic twins was investigated.

RESULTS

The mean value for daily concentration of air pollutants were 5.9 µg/m for PM, 16.3 ppb for O, 6.5 ppb for NO, and 1.4 ppb for SO, respectively. All air pollutants' levels in Brisbane during our study period were well under the National Air Quality Standard Air pollutant levels. We observed positive associations (false discovery rate [FDR]<0.1) among twins between PM and expression levels of HSPA8 and SOD1 and also between SO and AHR expression level. Negative associations were observed between SO and 11 genes among twins, including AHR, DUSP1, GEMIN4, GPX1, KLF2, PTGS2, TLR4, TNF, TNFRSF1B, TXNRD1, and XBP1, with most of them found at lag 0-7 days (FDR < 0.1). Furthermore, the association between SO and DUSP1 expression level was stronger among monozygotic twins than dizygotic twins (FDR < 0.1). We did not find strong evidence linking air pollutants to gene expression levels among parents.

CONCLUSION

Our findings require confirmation but suggest potential associations of expression levels at several genes with air pollutants at low exposure level and an individual's genetic background modifies the association between SO and DUSP1 gene, which may help bridge the gap of epidemiological studies with both in vivo and in vitro toxicological experiments and provide some insights into the role of nature-nurture of an individual in gene expression response to air pollutants.