A1 Vertaisarvioitu alkuperäisartikkeli tieteellisessä lehdessä
Liver DNA methylation of FADS2 associates with FADS2 genotype
Tekijät: Walle P, Männistö V, de Mello VD, Vaittinen M, Perfilyev A, Hanhineva K, Ling C, Pihlajamäki J
Julkaisuvuosi: 2019
Journal: Clinical Epigenetics
Tietokannassa oleva lehden nimi: Clinical epigenetics
Lehden akronyymi: Clin Epigenetics
Vuosikerta: 11
Numero: 1
Sivujen määrä: 9
ISSN: 1868-7075
eISSN: 1868-7083
DOI: https://doi.org/10.1186/s13148-019-0609-1
Tiivistelmä
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.\n) 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.\nWe 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.\nGenetic variants of FADS2 may contribute to the pathogenesis of non-alcoholic fatty liver disease by modifying DNA methylation.\nBACKGROUND\nMETHODS\nRESULTS\nCONCLUSIONS
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.\n) 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.\nWe 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.\nGenetic variants of FADS2 may contribute to the pathogenesis of non-alcoholic fatty liver disease by modifying DNA methylation.\nBACKGROUND\nMETHODS\nRESULTS\nCONCLUSIONS
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