Genetic aspects of susceptibility to air pollution

Kleeberger, Steven R.

doi:10.1183/09031936.03.00403003

Cited by 45 publications

(26 citation statements)

References 51 publications

(48 reference statements)

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“…Inter-individual variation in response to air pollution exposure is commonly reported in the published literature, and is likely to have, at least in part, a genetic basis (Kleeberger 2003;Yang et al 2008). The view that the underlying genetic/genomic context may be an important feature of individual and population level responses to air pollution is supported by the work of Rubes et al (2007), who used the SCSA assay to demonstrate that men who were homozygous for the GSTM1 deletion polymorphism were characterized by a higher percentage of sperm having DNA/ chromatin damage in response to intermittent air pollution.…”

Section: Genetic Variation and Inter-individual Response To Air Pollumentioning

confidence: 96%

Air pollution and mutations in the germline: are humans at risk?

Somers

Cooper

2008

Hum Genet

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Genotoxic air pollution is ubiquitous in urban and industrial areas. A variety of studies has linked human exposure to air pollution with a number of different somatic cell endpoints including cancer. However, the potential for inducing mutations in the human germline remains unclear. Sentinel animal studies of germline mutations at tandem-repeat loci (specifically minisatellites and expanded simple tandem repeats) have recently provided proof of principle that germline mutations can be induced in vertebrates (birds and mice) by air pollution under ambient conditions. Although humans may also be susceptible to induced germline mutations in polluted areas, uncertainties regarding causative agents, doses, and mutational mechanisms at repetitive DNA loci currently preclude extrapolation from animal data to the evaluation of human risk. Nevertheless, several recent studies have linked air pollution exposure to DNA damage in human sperm, indicating that our germ cells are not impervious to the genotoxic effects of air pollution. Thus, both sentinel animal and human studies have raised the possibility that ambient air pollution may increase human germline mutation rates, especially at repetitive DNA loci. Given that some human genetic conditions appear to be modulated by length mutations at tandem-repeat loci (e.g. HRAS1 cancers, type 1 diabetes, etc.), there is an urgent need for extensive study in this area. Research should be primarily focused upon: (1) the direct measurement of mutation frequencies at repetitive DNA loci in human male germ cells as a function of air pollution exposure, (2) large-scale epidemiology studies of inherited disorders and tandem-repeat associated genetic conditions and air pollution, and (3) the characterization of mutational mechanisms at hypervariable tandem-repeat loci.

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Section: Genetic Variation and Inter-individual Response To Air Pollumentioning

confidence: 96%

Air pollution and mutations in the germline: are humans at risk?

Somers

Cooper

2008

Hum Genet

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“…Variability in response to air pollution may be associated with genetic differences or polymorphisms that convey an increased risk for an individual. [62][63][64] Identification of susceptible subgroups of the population who may be particularly vulnerable to air pollution-induced health effects is critical in order to characterize and possibly mitigate potential contributors to interindividual variability and the burden of pulmonary diseases. 64 Due to the central role of inflammation and oxidative stress in the response to air pollution, genes that modulate inflammation and antioxidant defense mechanisms are considered to contribute to interindividual variability in response to air pollution.…”

Section: Ambient Air Pollutionmentioning

confidence: 99%

“…These studies report correlations between several hallmarks of respiratory health effects, including lung hyperpermeability, injury and inflammation, and genetic differences within these chromosomes. 62 Some of the candidate genes include those involved with inflammation, including TLR4, TNFA, glutathione peroxidase 1 (GPX1), and xanthine dehydrogenase (XDH); metabolizing enzymes, such as glutathione S-transferase mu 1 (GSTM1), glutathione S-transferase P1 (GSTP1) and nicotimamide adenine dinucleotide phosphate quinine oxidoreductase (NQO1); and other small inducible cytokines, many of which are activated through NF-κB transcription factor signaling. 62,64 There is evidence that GSTM1, present in the airways and completely absent in 50% of the population, may contribute to reduced lung function in deficient individuals.…”

Section: Ambient Air Pollutionmentioning

confidence: 99%

Impact of air pollution on lung inflammation and the role of Toll-like receptors

Plummer¹,

Smiley‐Jewell²,

Pinkerton³

2012

IJICMR

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Abstract:The link between air pollution and adverse pulmonary health effects is well established. The National Ambient Air Quality Standards were formulated to protect human health. These standards are strictly enforced based on strong associations between elevated air pollution levels and increased emergency room visits and hospitalizations due to respiratory conditions. Impacts of air pollution on lung health occur due to the direct interaction between the external environment and internal biological systems and processes. The innate immune system is one of the first lines of defense against inhaled air contaminants and is characterized by activation of key signaling pathways and inflammatory cell recruitment to the lung. Numerous independent and often redundant pathways participate in innate and adaptive immune responses. Given the impact of air pollution on human health, extensive research efforts have aimed to characterize the mechanisms of response to various air pollutants and evaluate risk factors contributing to individual susceptibility. A significant body of evidence exists to document air pollution-induced alterations in proinflammatory or oxidative signaling molecules. However, the role of specific pathways participating in the propagation of the inflammatory effects remains unclear. One hypothesis for interindividual susceptibility to inhaled air pollutants is that genetic polymorphisms in inflammatory or oxidative stress pathways may contribute to the diverse range of the inflammatory response. Activation of numerous receptors associated with airway cells culminates in the translocation of nuclear factor-kappa B and other transcription factors to the nucleus, and therefore initiation of altered signaling of proinflammatory mediators. Alterations in the transcription and expression of inflammatory mediators following exposure to air pollution are well documented. However, the interaction between specific air pollutants and specific cell surface and intracellular receptors has not been clearly defined. Involvement of specific pathways in the innate immune response may be dependent on differential physical and chemical characteristics of air pollution. One pathway implicated in the response to inhaled air pollutants is initiated by the activation of Toll-like receptors (TLRs). TLRs and downstream proinflammatory mediators are well studied for their role in pathogen response, yet gaps in the understanding of TLR response to nonpathogenic agents, such as air pollution, exist. TLRs are associated with inflammation and allergy, and emerging evidence suggests they may also play a role in the response and susceptibility to air pollution. However, the specific component, exogenous or endogenous, responsible for the association between air pollution and TLR activation has yet to be clearly identified. Improved understanding of pulmonary response mechanisms and potential mediators of susceptibility to air pollution, including the role of TLRs, may contribute to a reduction of the health burden of air pollutio...

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“…Environmental exposures to inhaled pollutants and genetic factors associated with disease risk likely interact in a complex fashion that varies from one population to another [2]. Investigations have suggested an influence of age on genetic susceptibility to lung cancer and other diseases, which indicate that an interaction between age and genetic background may be important in air pollution disease pathogenesis [3]. Tobacco smoke is an important contributor to the factors in the environment that impact on the health of individuals, including the fetus in the womb.…”

Section: Introductionmentioning

confidence: 99%

Transgenerational Effects of Maternal Nicotine Exposure During Gestation and Lactation on the Respiratory System

Maritz¹

2012

Point Mutation

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Genetic aspects of susceptibility to air pollution

Cited by 45 publications

References 51 publications

Air pollution and mutations in the germline: are humans at risk?

Air pollution and mutations in the germline: are humans at risk?

Impact of air pollution on lung inflammation and the role of Toll-like receptors

Transgenerational Effects of Maternal Nicotine Exposure During Gestation and Lactation on the Respiratory System

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