title: The effects of omega-3 polyunsaturated fatty acids and genetic variants on methylation levels of the interleukin-6 gene promoter.
abstract: METHODS
  Omega-3 PUFAs (n-3 PUFAs) reduce IL-6 gene expression, but their effects on transcription regulatory mechanisms are unknown. We aimed to conduct an integrated analysis with both population and in vitro studies to systematically explore the relationships among n-3 PUFA, DNA methylation, single nucleotide polymorphisms (SNPs), gene expression, and protein concentration of IL6.
  
  
  RESULTS
  Using data in the Genetics of Lipid Lowering Drugs and Diet Network (GOLDN) study and the Encyclopedia of DNA Elements (ENCODE) consortium, we found that higher methylation of IL6 promoter cg01770232 was associated with higher IL-6 plasma concentration (p = 0.03) and greater IL6 gene expression (p = 0.0005). Higher circulating total n-3 PUFA was associated with lower cg01770232 methylation (p = 0.007) and lower IL-6 concentration (p = 0.02). Moreover, an allele of IL6 rs2961298 was associated with higher cg01770232 methylation (p = 2.55 × 10(-7) ). The association between n-3 PUFA and cg01770232 methylation was dependent on rs2961298 genotype (p = 0.02), but higher total n-3 PUFA was associated with lower cg01770232 methylation in the heterozygotes (p = 0.04) not in the homozygotes.
  
  
  CONCLUSIONS
  Higher n-3 PUFA is associated with lower methylation at IL6 promoter, which may be modified by IL6 SNPs.
authors.affiliation: Jean Mayer US Department of Agriculture Human Nutrition Research Center on Aging, Tufts University, Boston, MA, USA.|Biomedical Genetics, Department of Medicine, Boston University, Boston, MA, USA.
authors.forename: Yiyi
authors.initials: Y
authors.lastname: Ma
authors.affiliation: Jean Mayer US Department of Agriculture Human Nutrition Research Center on Aging, Tufts University, Boston, MA, USA.
authors.forename: Caren E
authors.initials: CE
authors.lastname: Smith
authors.affiliation: Jean Mayer US Department of Agriculture Human Nutrition Research Center on Aging, Tufts University, Boston, MA, USA.
authors.forename: Chao-Qiang
authors.initials: CQ
authors.lastname: Lai
authors.affiliation: Department of Epidemiology, University of Alabama at Birmingham, Birmingham, AL, USA.
authors.forename: Marguerite R
authors.initials: MR
authors.lastname: Irvin
authors.affiliation: Jean Mayer US Department of Agriculture Human Nutrition Research Center on Aging, Tufts University, Boston, MA, USA.
authors.forename: Laurence D
authors.initials: LD
authors.lastname: Parnell
authors.affiliation: Jean Mayer US Department of Agriculture Human Nutrition Research Center on Aging, Tufts University, Boston, MA, USA.
authors.forename: Yu-Chi
authors.initials: YC
authors.lastname: Lee
authors.affiliation: Jean Mayer US Department of Agriculture Human Nutrition Research Center on Aging, Tufts University, Boston, MA, USA.
authors.forename: Lucia D
authors.initials: LD
authors.lastname: Pham
authors.affiliation: Department of Epidemiology, University of Alabama at Birmingham, Birmingham, AL, USA.
authors.forename: Stella
authors.initials: S
authors.lastname: Aslibekyan
authors.affiliation: Department of Epidemiology, University of Alabama at Birmingham, Birmingham, AL, USA.
authors.forename: Steven A
authors.initials: SA
authors.lastname: Claas
authors.affiliation: Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN, USA.
authors.forename: Michael Y
authors.initials: MY
authors.lastname: Tsai
authors.affiliation: Department of Genetics, Washington University School of Medicine, St. Louis, MO, USA.
authors.forename: Ingrid B
authors.initials: IB
authors.lastname: Borecki
authors.affiliation: Department of Medicine, Vanderbilt University, Nashville, TN, USA.
authors.forename: Edmond K
authors.initials: EK
authors.lastname: Kabagambe
authors.affiliation: Jean Mayer US Department of Agriculture Human Nutrition Research Center on Aging, Tufts University, Boston, MA, USA.|Department of Epidemiology, Centro Nacional Investigaciones Cardiovasculares (CNIC), Madrid, Spain.|Instituto Madrileño de Estudios Avanzados en Alimentación (IMDEA-FOOD), Madrid, Spain.
authors.forename: José M
authors.initials: JM
authors.lastname: Ordovás
authors.affiliation: Hudson Alpha Institute for Biotechnology, Huntsville, AL, USA.
authors.forename: Devin M
authors.initials: DM
authors.lastname: Absher
authors.affiliation: Department of Epidemiology, University of Alabama at Birmingham, Birmingham, AL, USA.
authors.forename: Donna K
authors.initials: DK
authors.lastname: Arnett
mesh_terms: D000328:Adult; D018899:CpG Islands; D019175:DNA Methylation / Q000187:drug effects*; D015525:Fatty Acids, Omega-3 / Q000097:blood / Q000494:pharmacology*; D005260:Female; D006801:Humans; D015850:Interleukin-6 / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic / Q000187:drug effects
chemical_list: D015525:Fatty Acids, Omega-3; C508600:IL6 protein, human; D015850:Interleukin-6
keywords: DNA methylation; Gene-by-environment interaction; Genetic variant; Interleukin-6; n-3 polyunsaturated fatty acids