Genetische Suszeptibilitäten gegenüber Luftschadstoff-induzierter altersbedingter Merkmale
Zusammenfassung der Projektergebnisse
This project leveraged from longitudinal data from the SALIA study. The project could show that genetic susceptibility plays an important role in air pollution-induced aging traits. We identified several risk variants which interacted with air pollution on the respiratory system and skin-related outcomes. In particular, we could show the beneficial effect of improved air quality on lung function in elderly women. In addition, the analysis on lung function revealed that the beneficial effects of improved air quality also depended on a person’s genetics. Carriers of more lung function-related risk alleles benefited less from improved air quality. In a second analysis the role of the endoplasmatic reticulum (ER) stress pathway was investigated. We could validate the association between risk alleles of SNPs of ER stress pathway and increased levels of airway inflammation (LTB4, TNF-α, total number of cells and NO derivatives). These results indicate that the combination of risk alleles of different SNPs of the ER stress pathway plays a major role for airway inflammation than the single SNPs on their own. Further, we could show that genetic variation in the unfolded protein response (UPR) modifies the association between air pollution exposure and subclinical airway inflammation in induced sputum. These results indicate that genetic variation in the ER stress pathway might play a role in air pollution induced inflammation in the lung. Little is known about the eczema phenotype in middle aged or elderly adults, or about the contribution of air pollution in this age group. Genetic and environmental risk factors both contribute the eczema development in children. Our results indicate that eczema in the elderly is a frequent medical problem in individuals older than 55. It is likely to be partly caused by air pollution, and differs from genetically driven atopic dermatitis, which is the most common type of eczema in children. Gene-environment interaction analysis on air pollution induced facial lentigines in German and Chinese women could show that genetic variations of the AHR/AHRR genes play a role for lentigines development in German as well as in Chinese. Analysis in both cohorts indicated that genetic variations in the AHR/AHRR signaling pathway and in the DNA repair enzyme MGMT are relevant for the development of facial lentigines. We therefore identified two previously unrecognized genetic variants to be involved in pigment spots formation in Caucasians and Han Chinese. From this study we also conclude that gene/environment interactions for air pollution and pigment spots formation depend on a given ethnic background. In conclusion we could show that the identified genes explain only a fraction of disease heritability and the investigation of additional environmental and lifestyle factors is needed.
Projektbezogene Publikationen (Auswahl)
- Genetic susceptibility for air pollution-induced airway inflammation in the SALIA study. Environ Res. 2017 Jan;152:43-50
Hüls A, Krämer U, Herder C, Fehsel K, Luckhaus C, Stolz S, Vierkötter A, Schikowski T
(Siehe online unter https://doi.org/10.1016/j.envres.2016.09.028) - Benefits of improved air quality on ageing lungs: impacts of genetics and obesity. Eur Respir J. 2019 Apr 25;53(4):1801780
Hüls A, Sugiri D, Abramson MJ, Hoffmann B, Schwender H, Ickstadt K, Krämer U, Schikowski T
(Siehe online unter https://doi.org/10.1183/13993003.01780-2018) - Nonatopic eczema in elderly women: Effect of air pollution and genes. J Allergy Clin Immunol. 2019 Jan;143(1):378-385.e9
Hüls A, Abramson MJ, Sugiri D, Fuks K, Krämer U, Krutmann J, Schikowski T
(Siehe online unter https://doi.org/10.1016/j.jaci.2018.09.0312017)
