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Genetic and methyla...
Genetic and methylation variation in the CYP2B6 gene is related to circulating p,p'-dde levels in a population-based sample
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Lind, Lars (författare)
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Ng, Esther (författare)
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Ingelsson, Erik (författare)
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Lindgren, Cecilia (författare)
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Salihovic, Samira (författare)
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van Bavel, Bert (författare)
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Mahajan, Anubha (författare)
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Lampa, Erik (författare)
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Morris, Andrew P (författare)
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Lind, P. Monica (författare)
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- 2017
- 2017
- Engelska.
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Ingår i: Environment International. - 0160-4120. ; 98, 212-218
Abstract
Ämnesord
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- OBJECTIVES: Since 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,p'-DDE, were related to genome-wide genetic and methylation variation in a population-based sample. METHODS: In the population-based Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study (1016 subjects all aged 70), circulating levels of p,p'-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. RESULTS: Evidence for genome-wide significant association with p,p'-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 472ng/g lipid, while the corresponding level for those being homozygote for the T allele was 192ng/g lipid (p=1.5×10(-31)). An analysis conditioned on the lead SNP disclosed a distinct signal in the same gene (rs7255374, position chr19:41520351; p=2.2×10(-8)). A whole-genome methylation analysis showed one significant relationship vs. p,p'-DDE levels (p=6.2×10(-9)) located 7kb downstream the CYP2B6 gene (cg27089200, position chr19:41531976). This CpG-site was also related to the lead SNP (p=3.8×10(-35)), but mediated only 4% of the effect of the lead SNP on p,p'-DDE levels. CONCLUSION: Circulating levels of p,p'-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,p'-DDE levels.
Ämnesord
- Medical and Health Sciences (hsv)
- Basic Medicine (hsv)
- Medical Genetics (hsv)
- Medicin och hälsovetenskap (hsv)
- Medicinska grundvetenskaper (hsv)
- Medicinsk genetik (hsv)
- Medical and Health Sciences (hsv)
- Health Sciences (hsv)
- Environmental Health and Occupational Health (hsv)
- Medicin och hälsovetenskap (hsv)
- Hälsovetenskaper (hsv)
- Miljömedicin och yrkesmedicin (hsv)
Nyckelord
- CYP2B6
- DDE
- GWAS
- Metabolism
- Methylation
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Till lärosätets databas
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Lind, Lars
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Ng, Esther
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Ingelsson, Erik
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Lindgren, Cecili ...
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Salihovic, Samir ...
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van Bavel, Bert
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visa fler...
-
Mahajan, Anubha
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Lampa, Erik
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Morris, Andrew P
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Lind, P. Monica
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visa färre...
- Av lärosätet
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