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The effects of omega‐3 polyunsaturated fatty acids and genetic variants on methylation levels of the interleukin‐6 gene promoter
Author(s) -
Ma Yiyi,
Smith Caren E.,
Lai ChaoQiang,
Irvin Marguerite R.,
Parnell Laurence D.,
Lee YuChi,
Pham Lucia D.,
Aslibekyan Stella,
Claas Steven A.,
Tsai Michael Y.,
Borecki Ingrid B.,
Kabagambe Edmond K.,
Ordovás José M.,
Absher Devin M.,
Arnett Donna K.
Publication year - 2016
Publication title -
molecular nutrition and food research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.495
H-Index - 131
eISSN - 1613-4133
pISSN - 1613-4125
DOI - 10.1002/mnfr.201500436
Subject(s) - methylation , dna methylation , single nucleotide polymorphism , promoter , polyunsaturated fatty acid , biology , gene , microbiology and biotechnology , genetics , allele , genotype , gene expression , fatty acid , biochemistry
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.