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Filaggrin variation...
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Wahlberg, K.Lund University,Lunds universitet,Avdelningen för arbets- och miljömedicin,Institutionen för laboratoriemedicin,Medicinska fakulteten,Division of Occupational and Environmental Medicine, Lund University,Department of Laboratory Medicine,Faculty of Medicine
(författare)
Filaggrin variations are associated with PAH metabolites in urine and DNA alterations in blood
- Artikel/kapitelEngelska2019
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LIBRIS-ID:oai:gup.ub.gu.se/284142
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https://gup.ub.gu.se/publication/284142URI
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https://doi.org/10.1016/j.envres.2019.108600DOI
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https://lup.lub.lu.se/record/f7433650-9b53-4a52-8e7b-a2b3b13de0c5URI
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http://kipublications.ki.se/Default.aspx?queryparsed=id:141807211URI
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Dermal chemical exposure is common in many professions. The filaggrin protein is important for the skin barrier and variations in the filaggrin gene (FLG) may influence the uptake of chemicals via the skin, and consequently, the degree of systemic effects. The aim of this study was to investigate, in chimney sweeps with occupational exposure to polycyclic aromatic hydrocarbons (PAH) from soot, the influence of variation in FLG on internal PAH dose and DNA alterations, including epigenetic, previously linked to cancer and cardiovascular disease. We used TaqMan PCR to genotype 151 chimney sweeps and 152 controls for four FLG null variants (R501X, R2447X, S3247X and 2282del4) which cause impaired skin barrier, and FLG copy number variation (12th repeat, CNV12) which potentially is beneficial for the skin barrier. The internal dose of PAH was represented by urinary PAH metabolites (e.g. 1-hydroxypyrene and 3-hydroxybenzo[a]pyrene) that we measured by LC-MS/MS. We measured epigenetic alterations (methylation of AHRR and F2RL3) in blood by pyrosequencing; and DNA alterations (telomere length and mitochondrial DNA copy number) by real-time PCR. Hypomethylation of AHRR or F2RL3 is a risk factor for lung cancer and shorter telomere length a risk factor for cardiovascular disease. The frequencies of FLG null were 8.6 and 11.8% (p = 0.35), and CNV12 27.8 and 19.7% (p = 0.09) in chimney sweeps and controls, respectively. We found that among chimney sweeps working predominately with soot sweeping (high PAH exposure), CNV12 carriers had lower concentrations of PAH metabolites in urine compared with non-carriers (median 1-hydroxypyrene = 0.37 vs 0.86 μg/g creatinine respectively; p = 0.025 by linear regression models adjusted for age, BMI and smoking) compared to sweeps not carrying CNV12. Further, FLG null was associated with approximately 2.5% higher methylation of F2RL3 (cg03636183, p = 0.019 after adjustment for exposure group, age, BMI and smoking). FLG null was associated with approximately 7% shorter telomere length (p = 0.015, adjusted model). Our results suggest that FLG variations may influence the dose of PAH in highly exposed workers, possibly via dermal uptake. It also suggests that FLG variation may influence the degree of (epi)genotoxicity in the body. FLG variation is common in the working population and should be considered in risk assessment. © 2019
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Liljedahl, Emelie RietzLund University,Lunds universitet,Avdelningen för arbets- och miljömedicin,Institutionen för laboratoriemedicin,Medicinska fakulteten,Division of Occupational and Environmental Medicine, Lund University,Department of Laboratory Medicine,Faculty of Medicine(Swepub:lu)med-ebn
(författare)
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Alhamdow, A.Karolinska Institutet,Karolinska Institute(Swepub:lu)med-aa10
(författare)
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Lindh, ChristianLund University,Lunds universitet,Avdelningen för arbets- och miljömedicin,Institutionen för laboratoriemedicin,Medicinska fakulteten,Division of Occupational and Environmental Medicine, Lund University,Department of Laboratory Medicine,Faculty of Medicine(Swepub:lu)ymed-cli
(författare)
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Lidén, C.Karolinska Institutet,Karolinska Institute
(författare)
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Albin, M.Karolinska Institutet,Karolinska Institute,Lund University,Lunds universitet,Avdelningen för arbets- och miljömedicin,Institutionen för laboratoriemedicin,Medicinska fakulteten,Arbetsorganisation och hälsa,Forskargrupper vid Lunds universitet,Division of Occupational and Environmental Medicine, Lund University,Department of Laboratory Medicine,Faculty of Medicine,Environmental health and occupational health,Lund University Research Groups(Swepub:lu)ymed-mal
(författare)
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Tinnerberg, Håkan,1965University of Gothenburg,Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för samhällsmedicin och folkhälsa, enheten för arbets-och miljömedicin,Institute of Medicine, Department of Public Health and Community Medicine, Section of Occupational and environmental medicine,Sahlgrenska Academy(Swepub:lu)ymed-hti
(författare)
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Broberg, K.Karolinska Institutet,Karolinska Institute,Lund University,Lunds universitet,Avdelningen för arbets- och miljömedicin,Institutionen för laboratoriemedicin,Medicinska fakulteten,Division of Occupational and Environmental Medicine, Lund University,Department of Laboratory Medicine,Faculty of Medicine(Swepub:lu)kgen-kbr
(författare)
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Avdelningen för arbets- och miljömedicinInstitutionen för laboratoriemedicin
(creator_code:org_t)
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Ingår i:Environmental Research: Elsevier BV1770013-93511096-0953
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