Genetic variants in autophagy associated genes are associated with DNA damage levels in Chinese population
Introduction
In recent years, air pollution has become a serious threat to human health (Ouyang, 2013). Epidemiology studies suggested that air pollution contributed to the increased morbidity and mortality of respiratory diseases, including lung cancer, chronic obstructive pulmonary disease (COPD), asthma and so on (Zhou et al., 2015, Guo et al., 2016, Fisher et al., 2016).
DNA damage is a common event which can be generated from environmental agents (such as ultraviolet light, ionizing radiation) and internal factors (such as reactive oxygen) (Jackson and Bartek, 2009). Many studies have demonstrated that unrepaired DNA damage played a key role in the process of cancer development (Jackson and Bartek, 2009, Hoeijmakers, 2009). Currently, one of the most important air pollutions in China is the accumulation of PM2.5. PM2.5 is also named fine particulate matter whose aerodynamic diameter ≤ 2.5 μm. Studies have shown that PM2.5 contributed to the risk of respiratory and cardiovascular diseases (Brook and Rajagopalan, 2010, McGuinn et al., 2016). PM2.5 is easy to absorb some organic chemicals, heavy metals and so forth. Many researches have proved that PM2.5 could aggravate DNA damage, oxygen free radicals induced by heavy metals and other substances or the formation of PAH-DNA adducts may be the potential mechanisms (Topinka et al., 2011, Deng et al., 2013, Hu et al., 2008, Perera et al., 2011). However, people who exposed to the similar environment may have different DNA damage levels, which indicated that genetic variants could also modify the DNA damage (Chu et al., 2015, Huang et al., 2012).
Autophagy is a crucial cellular process. Oxidative stress, starvation and diversified other stimuli could regulate this response (Rodriguez-Rocha et al., 2011). During this process, cell solute and organelles were wrapped up within double-membrane vesicles which would be carried to the lysosome or vacuole (Klionsky, 2005). Previous studies have demonstrated that autophagy could modify DNA damage repair, and the disorder of autophagy might result in the accumulation of DNA damage through the increase of oxidative stress and other mechanisms (Jin and White, 2007, Panda et al., 2015).
Based on these studies, we assumed that polymorphisms in ATGs could regulate DNA damage levels. In order to validate our hypothesis, 307 subjects were recruited from three different cities (Zhuhai, Wuhan and Tianjin) in China, relevant information, such as demographic data, 24-h PM2.5 exposure levels were collected. Seven potentially functional polymorphisms in four selected essential autophagy associated genes (ATG5, ATG7, ATG8, ATG13) were screened to evaluate the relationship between the polymorphism of autophagy associated genes and DNA damage by using multivariable linear regression model.
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Study subjects
In the beginning, 328 subjects were enrolled in this research. All of these subjects were from three different cities (Zhuhai: 119; Wuhan: 123; Tianjin: 86), detailed information about the subjects please refer to our previous papers (Gong et al., 2014, Liu et al., 2016). Briefly, all participants were interviewed to gather demographic data and epidemiological information. Gilian 5000 pumps were used to measure individual 24-h PM2.5 exposure levels. 21 participants were further excluded because
Baseline information of 307 subjects
The basic information and epidemiological information are summarized in Supplementary Table 1. PM2.5 exposure levels in three cities were different (median value: 68.35 μg/m3 (Zhuhai), 114.96 μg/m3 (Wuhan) and 146.60 μg/m3 (Tianjin)). The median percentages of tail DNA are 1.36% (Zhuhai), 1.85% (Wuhan) and 2.97% (Tianjin) respectively in three cities. And we then divided all the participants into four groups according to the quartile of PM2.5 exposure levels to study the relationship between
Discussion
This study aimed to explore the relationship between genetic variants in ATGs and DNA damage. Seven potentially functional polymorphisms in these four ATGs were included in this study, and two SNPs (rs12599322 and rs7484002) were identified to be associated with DNA damage levels.
In our previous studies, we explored the association between genetic variants in SMARC and multisynthetase complex genes and DNA damage levels (Gong et al., 2014, Liu et al., 2016). We successfully identified several
Author disclosure statement
The authors declare that they do not have competing financial interest.
Acknowledgments
This work was funded by the National Key Basic Research Program Grant (2011CB503805), the National Natural Science Foundation of China (81521004, 81230067, 81390543), the Priority Academic Program for the Development of Jiangsu Higher Education Institutions [Public Health and Preventive Medicine] and Top-notch Academic Programs Project of Jiangsu Higher Education Institutions (PPZY2015A067). The authors are grateful to all the study participants.
References (34)
- et al.
Personal exposure to PM2.5, genetic variants and DNA damage: a multi-center population-based study in Chinese
Toxicol. Lett.
(2015) - et al.
PM2.5-induced oxidative stress triggers autophagy in human lung epithelial A549 cells
Toxicology in vitro : an international journal published in association with BIBRA
(2013) - et al.
Genetic variants in SMARC genes are associated with DNA damage levels in Chinese population
Toxicol. Lett.
(2014) - et al.
The association between lung cancer incidence and ambient air pollution in China: a spatiotemporal analysis
Environ. Res.
(2016) - et al.
Genetic variations of CYP2B6 gene were associated with plasma BPDE-Alb adducts and DNA damage levels in coke oven workers
Toxicol. Lett.
(2012) - et al.
Genetic variants in multisynthetase complex genes are associated with DNA damage levels in Chinese populations
Mutat. Res.
(2016) - et al.
Association between satellite-based estimates of long-term PM2.5 exposure and coronary artery disease
Environ. Res.
(2016) China wakes up to the crisis of air pollution
Lancet Respir. Med.
(2013)- et al.
Mechanism of autophagic regulation in carcinogenesis and cancer therapeutics
Semin. Cell Dev. Biol.
(2015) - et al.
DNA damage and autophagy
Mutat. Res.
(2011)
DNA adducts and oxidative DNA damage induced by organic extracts from PM2.5 in an acellular assay
Toxicol. Lett.
The associations between ambient air pollution and adult respiratory mortality in 32 major Chinese cities, 2006–2010
Environ. Res.
The effect of phenotypic outliers and non-normality on rare-variant association testing
Eur. J. Hum. Genet.: EJHG
The essential comet assay: a comprehensive guide to measuring DNA damage and repair
Arch. Toxicol.
Testing the significance of a correlation with nonnormal data: comparison of Pearson, spearman, transformation, and resampling approaches
Psychol. Methods
Particulate matter air pollution and atherosclerosis
Current atherosclerosis reports
Autophagy in DNA damage response
Int. J. Mol. Sci.
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These authors contributed equally to this work.