کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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5748474 | 1619032 | 2017 | 7 صفحه PDF | دانلود رایگان |
- A whole genome scan was used to investigate the metabolic route of p,pâ²-DDE in human.
- Genetic variation in the CYP2B6 gene was associated with p,pâ²-DDE levels.
- Methylation close to the same gene was associated with p,pâ²-DDE levels.
- Modern genetic analyses showed CYP2B6 to be linked to p,pâ²-DDE levels in human.
ObjectivesSince the metabolism of the organochlorine pesticide dichlorodiphenyltrichloroethane (DDT) is not fully known in humans, we evaluated if circulating levels of a major breakdown product of DDT, p,pâ²-DDE, were related to genome-wide genetic and methylation variation in a population-based sample.MethodsIn the population-based Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study (1016 subjects all aged 70), circulating levels of p,pâ²-DDE were analyzed by high-resolution chromatography coupled to high-resolution mass spectrometry (HRGC/HRMS). Genetic variants were genotyped and imputed (1000 Genomes reference, March 2012 release). Methylation sites were assayed using the Illumina HumanMethylation450 array in whole blood. A genome-wide association study (GWAS) approach was applied.ResultsEvidence for genome-wide significant association with p,pâ²-DDE levels was observed only for a locus at chromosome 19 corresponding to the CYP2B6 gene (lead SNP rs7260538). Subjects being homozygote for the G allele showed a median level of 472 ng/g lipid, while the corresponding level for those being homozygote for the T allele was 192 ng/g lipid (p = 1.5 Ã 10â 31). An analysis conditioned on the lead SNP disclosed a distinct signal in the same gene (rs7255374, position chr19:41520351; p = 2.2 Ã 10â 8).A whole-genome methylation analysis showed one significant relationship vs. p,pâ²-DDE levels (p = 6.2 Ã 10â 9) located 7 kb downstream the CYP2B6 gene (cg27089200, position chr19:41531976). This CpG-site was also related to the lead SNP (p = 3.8 Ã 10â 35), but mediated only 4% of the effect of the lead SNP on p,pâ²-DDE levels.ConclusionCirculating levels of p,pâ²-DDE were related to genetic variation in the CYP2B6 gene in the general elderly population. DNA methylation in this gene is not closely linked to the p,pâ²-DDE levels.
Journal: Environment International - Volume 98, January 2017, Pages 212-218