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Liver DNA methylation of FADS2 associates with FADS2 genotypex 06 Biological Sciences 0604 Genetics

Walle, Paula ; Männistö, Ville ; De Mello, Vanessa Derenji ; Vaittinen, Maija ; Perfilyev, Alexander LU orcid ; Hanhineva, Kati ; Ling, Charlotte LU orcid and Pihlajamäki, Jussi (2019) In Clinical Epigenetics 11(1).
Abstract

Background: Non-alcoholic fatty liver disease has been associated with increased mRNA expression of FADS2 in the liver and estimated activity of delta-6 desaturase in serum, encoded by the FADS2 gene. Since DNA methylation in the FADS1/2/3 gene cluster has been previously linked with genetic variants and desaturase activities, we now aimed to discover factors regulating DNA methylation of the CpG sites annotated to FADS1/2 genes. Methods: DNA methylation levels in the CpG sites annotated to FADS2 and FADS1 were analyzed from liver samples of 95 obese participants of the Kuopio Obesity Surgery Study (34 men and 61 women, age 49.5 ± 7.7 years, BMI 43.0 ± 5.7 kg/m2) using the Infinium HumanMethylation450 BeadChip (Illumina).... (More)

Background: Non-alcoholic fatty liver disease has been associated with increased mRNA expression of FADS2 in the liver and estimated activity of delta-6 desaturase in serum, encoded by the FADS2 gene. Since DNA methylation in the FADS1/2/3 gene cluster has been previously linked with genetic variants and desaturase activities, we now aimed to discover factors regulating DNA methylation of the CpG sites annotated to FADS1/2 genes. Methods: DNA methylation levels in the CpG sites annotated to FADS2 and FADS1 were analyzed from liver samples of 95 obese participants of the Kuopio Obesity Surgery Study (34 men and 61 women, age 49.5 ± 7.7 years, BMI 43.0 ± 5.7 kg/m2) using the Infinium HumanMethylation450 BeadChip (Illumina). Associations between DNA methylation levels and estimated delta-6 and delta-5 desaturase enzyme activities, liver histology, hepatic mRNA expression, FADS1/2 genotypes, and erythrocyte folate levels were analyzed. Results: We found a negative correlation between DNA methylation levels of cg06781209 and cg07999042 and hepatic FADS2 mRNA expression (both p < 0.05), and with estimated delta-6 desaturase activity based on both liver and serum fatty acids (all p < 0.05). Interestingly, the methylation level of cg07999042 (p = 0.001) but not of cg06781209 (p = 0.874) was associated with FADS2 variant rs174616. Conclusions: Genetic variants of FADS2 may contribute to the pathogenesis of non-alcoholic fatty liver disease by modifying DNA methylation.

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author
; ; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Delta-6 desaturase, DNA methylation, Epigenetics, FADS2, Liver, mRNA expression, Non-alcoholic fatty liver disease
in
Clinical Epigenetics
volume
11
issue
1
article number
10
publisher
BioMed Central (BMC)
external identifiers
  • scopus:85060130926
  • pmid:30654845
ISSN
1868-7075
DOI
10.1186/s13148-019-0609-1
language
English
LU publication?
yes
id
c5546017-46e7-422a-86fa-fe3b0254fc28
date added to LUP
2019-01-28 14:53:18
date last changed
2024-03-02 18:12:10
@article{c5546017-46e7-422a-86fa-fe3b0254fc28,
  abstract     = {{<p>Background: Non-alcoholic fatty liver disease has been associated with increased mRNA expression of FADS2 in the liver and estimated activity of delta-6 desaturase in serum, encoded by the FADS2 gene. Since DNA methylation in the FADS1/2/3 gene cluster has been previously linked with genetic variants and desaturase activities, we now aimed to discover factors regulating DNA methylation of the CpG sites annotated to FADS1/2 genes. Methods: DNA methylation levels in the CpG sites annotated to FADS2 and FADS1 were analyzed from liver samples of 95 obese participants of the Kuopio Obesity Surgery Study (34 men and 61 women, age 49.5 ± 7.7 years, BMI 43.0 ± 5.7 kg/m<sup>2</sup>) using the Infinium HumanMethylation450 BeadChip (Illumina). Associations between DNA methylation levels and estimated delta-6 and delta-5 desaturase enzyme activities, liver histology, hepatic mRNA expression, FADS1/2 genotypes, and erythrocyte folate levels were analyzed. Results: We found a negative correlation between DNA methylation levels of cg06781209 and cg07999042 and hepatic FADS2 mRNA expression (both p &lt; 0.05), and with estimated delta-6 desaturase activity based on both liver and serum fatty acids (all p &lt; 0.05). Interestingly, the methylation level of cg07999042 (p = 0.001) but not of cg06781209 (p = 0.874) was associated with FADS2 variant rs174616. Conclusions: Genetic variants of FADS2 may contribute to the pathogenesis of non-alcoholic fatty liver disease by modifying DNA methylation.</p>}},
  author       = {{Walle, Paula and Männistö, Ville and De Mello, Vanessa Derenji and Vaittinen, Maija and Perfilyev, Alexander and Hanhineva, Kati and Ling, Charlotte and Pihlajamäki, Jussi}},
  issn         = {{1868-7075}},
  keywords     = {{Delta-6 desaturase; DNA methylation; Epigenetics; FADS2; Liver; mRNA expression; Non-alcoholic fatty liver disease}},
  language     = {{eng}},
  month        = {{01}},
  number       = {{1}},
  publisher    = {{BioMed Central (BMC)}},
  series       = {{Clinical Epigenetics}},
  title        = {{Liver DNA methylation of FADS2 associates with FADS2 genotypex 06 Biological Sciences 0604 Genetics}},
  url          = {{http://dx.doi.org/10.1186/s13148-019-0609-1}},
  doi          = {{10.1186/s13148-019-0609-1}},
  volume       = {{11}},
  year         = {{2019}},
}