05111nas a2200877 4500008004100000022001400041245025000055210006900305260001300374300001100387490000800398520248000406653002202886653003902908653002102947653001902968653000902987653002002996653002603016653002403042653001603066653003103082653001103113653001103124653003603135653003003171653001803201100001303219700002003232700002003252700002003272700002403292700001903316700002103335700001403356700001703370700001303387700001903400700002103419700002303440700002003463700002303483700002103506700002003527700002803547700002303575700001503598700002203613700002103635700001303656700002503669700002003694700002503714700001603739700002203755700002603777700002003803700001903823700002503842700002203867700002503889700002103914700002003935700002003955700002503975700001704000700002204017700003004039700002004069700002404089700001804113700002104131700002104152700002404173856003604197 2016 eng d a1938-320700aInteraction of methylation-related genetic variants with circulating fatty acids on plasma lipids: a meta-analysis of 7 studies and methylation analysis of 3 studies in the Cohorts for Heart and Aging Research in Genomic Epidemiology consortium.0 aInteraction of methylationrelated genetic variants with circulat c2016 Feb a567-780 v1033 a
BACKGROUND: DNA methylation is influenced by diet and single nucleotide polymorphisms (SNPs), and methylation modulates gene expression.
OBJECTIVE: We aimed to explore whether the gene-by-diet interactions on blood lipids act through DNA methylation.
DESIGN: We selected 7 SNPs on the basis of predicted relations in fatty acids, methylation, and lipids. We conducted a meta-analysis and a methylation and mediation analysis with the use of data from the CHARGE (Cohorts for Heart and Aging Research in Genomic Epidemiology) consortium and the ENCODE (Encyclopedia of DNA Elements) consortium.
RESULTS: On the basis of the meta-analysis of 7 cohorts in the CHARGE consortium, higher plasma HDL cholesterol was associated with fewer C alleles at ATP-binding cassette subfamily A member 1 (ABCA1) rs2246293 (β = -0.6 mg/dL, P = 0.015) and higher circulating eicosapentaenoic acid (EPA) (β = 3.87 mg/dL, P = 5.62 × 10(21)). The difference in HDL cholesterol associated with higher circulating EPA was dependent on genotypes at rs2246293, and it was greater for each additional C allele (β = 1.69 mg/dL, P = 0.006). In the GOLDN (Genetics of Lipid Lowering Drugs and Diet Network) study, higher ABCA1 promoter cg14019050 methylation was associated with more C alleles at rs2246293 (β = 8.84%, P = 3.51 × 10(18)) and lower circulating EPA (β = -1.46%, P = 0.009), and the mean difference in methylation of cg14019050 that was associated with higher EPA was smaller with each additional C allele of rs2246293 (β = -2.83%, P = 0.007). Higher ABCA1 cg14019050 methylation was correlated with lower ABCA1 expression (r = -0.61, P = 0.009) in the ENCODE consortium and lower plasma HDL cholesterol in the GOLDN study (r = -0.12, P = 0.0002). An additional mediation analysis was meta-analyzed across the GOLDN study, Cardiovascular Health Study, and the Multi-Ethnic Study of Atherosclerosis. Compared with the model without the adjustment of cg14019050 methylation, the model with such adjustment provided smaller estimates of the mean plasma HDL cholesterol concentration in association with both the rs2246293 C allele and EPA and a smaller difference by rs2246293 genotypes in the EPA-associated HDL cholesterol. However, the differences between 2 nested models were NS (P > 0.05).
CONCLUSION: We obtained little evidence that the gene-by-fatty acid interactions on blood lipids act through DNA methylation.
10aApolipoproteins E10aATP Binding Cassette Transporter 110aCholesterol, HDL10aCohort Studies10aDiet10aDNA Methylation10aEicosapentaenoic Acid10aEpigenesis, Genetic10aFatty Acids10aGene Expression Regulation10aHumans10aLipids10aPolymorphism, Single Nucleotide10aPromoter Regions, Genetic10aTriglycerides1 aMa, Yiyi1 aFollis, Jack, L1 aSmith, Caren, E1 aTanaka, Toshiko1 aManichaikul, Ani, W1 aChu, Audrey, Y1 aSamieri, Cecilia1 aZhou, Xia1 aGuan, Weihua1 aWang, Lu1 aBiggs, Mary, L1 aChen, Yii-der, I1 aHernandez, Dena, G1 aBorecki, Ingrid1 aChasman, Daniel, I1 aRich, Stephen, S1 aFerrucci, Luigi1 aIrvin, Marguerite, Ryan1 aAslibekyan, Stella1 aZhi, Degui1 aTiwari, Hemant, K1 aClaas, Steven, A1 aSha, Jin1 aKabagambe, Edmond, K1 aLai, Chao-Qiang1 aParnell, Laurence, D1 aLee, Yu-Chi1 aAmouyel, Philippe1 aLambert, Jean-Charles1 aPsaty, Bruce, M1 aKing, Irena, B1 aMozaffarian, Dariush1 aMcKnight, Barbara1 aBandinelli, Stefania1 aTsai, Michael, Y1 aRidker, Paul, M1 aDing, Jingzhong1 aMstat, Kurt, Lohmant1 aLiu, Yongmei1 aSotoodehnia, Nona1 aBarberger-Gateau, Pascale1 aSteffen, Lyn, M1 aSiscovick, David, S1 aAbsher, Devin1 aArnett, Donna, K1 aOrdovas, Jose, M1 aLemaitre, Rozenn, N uhttps://chs-nhlbi.org/node/6951