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DNA methylation in an enhancer region of the FADS cluster is associated with FADS activity in human liver (373.8)
Author(s) -
Chilton Floyd,
Mathias Rasika,
Seeds Michael,
Herrington David,
Hixson James,
Hawkins Greg,
Sergeant Susan,
Miller Leslie,
Howard Timothy
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.373.8
Subject(s) - fads2 , biology , dna methylation , eicosapentaenoic acid , genetics , docosahexaenoic acid , polyunsaturated fatty acid , biochemistry , fatty acid , gene , gene expression
Omega‐6 (n‐6) and omega‐3 (n‐3), long chain polyunsaturated fatty acids (LcPUFAs) impact a wide range of biological activities ranging from immune signaling to brain function. Two desaturase steps (Δ6, encoded by FADS2 and Δ5, encoded by FADS1) are rate‐limiting in the conversion of dietary essential 18 carbon PUFAs such as linoleic acid (n‐6) to arachidonic acid and α‐linolenic acid (n‐3) to eicosapentaenoic and docosahexaenoic acids. Genetic variants in and around FADS1 and FADS2 are highly associated with levels of LcPUFAs as well as cardiovascular disease risk factors. Particularly, rs174537 is associated with both FADS activity and circulating AA levels (p = 5.95 x 10‐46). FADS1 and FADS2 sit adjacent (5’ to 5’) on chromosome 11 (11q12.2). We hypothesized that SNPs such as rs174537 were associated with DNA methylation variation that impacted LcPUFA levels and FADS activities. To test this hypothesis, we performed a genome‐wide allele‐specific methylation study with rs174537 in 144 human liver samples. This approach identified a strong association of rs174537 with CpG sites in an enhancer region between FADS1 and FADS2 (p=2.69x10‐29). These data suggested that rs174537 was serving as a genetic proxy for methylation variability in a critical enhancer region sitting between two proximal promoters for FADS1 and FADS2. Importantly, methylation levels of the significant probes were shown to be strongly associated with FADS1 and FADS2 activities within the liver. Grant Funding Source : NIH ‐ P50 AT002782