The effects of omega-3 polyunsaturated fatty acids and genetic variants on methylation levels of the interleukin-6 gene promoter

Yiyi Ma, Caren E. Smith, Chao Qiang Lai, Marguerite R. Irvin, Laurence D. Parnell, Yu Chi Lee, Lucia D. Pham, Stella Aslibekyan, Steven A. Claas, Michael Y. Tsai, Ingrid B. Borecki, Edmond K. Kabagambe, José M. Ordovás, Devin M. Absher, Donna K. Arnett

Research output: Contribution to journalArticlepeer-review

15 Scopus citations

Abstract

Scope: 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. Methods and 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. Conclusion: Higher n-3 PUFA is associated with lower methylation at IL6 promoter, which may be modified by IL6 SNPs.

Original languageEnglish (US)
Pages (from-to)410-419
Number of pages10
JournalMolecular Nutrition and Food Research
Volume60
Issue number2
DOIs
StatePublished - Feb 1 2016

Bibliographical note

Publisher Copyright:
© 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Keywords

  • DNA methylation
  • Gene-by-environment interaction
  • Genetic variant
  • Interleukin-6
  • n-3 polyunsaturated fatty acids

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