|Title||Interaction 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.|
|Publication Type||Journal Article|
|Year of Publication||2016|
|Authors||Ma Y, Follis JL, Smith CE, Tanaka T, Manichaikul AW, Chu AY, Samieri C, Zhou X, Guan W, Wang L, Biggs ML, Chen Y-DI, Hernandez DG, Borecki I, Chasman DI, Rich SS, Ferrucci L, Irvin MRyan, Aslibekyan S, Zhi D, Tiwari HK, Claas SA, Sha J, Kabagambe EK, Lai C-Q, Parnell LD, Lee Y-C, Amouyel P, Lambert J-C, Psaty BM, King IB, Mozaffarian D, McKnight B, Bandinelli S, Tsai MY, Ridker PM, Ding J, Mstat KLohmant, Liu Y, Sotoodehnia N, Barberger-Gateau P, Steffen LM, Siscovick DS, Absher D, Arnett DK, Ordovas JM|
|Secondary Authors||Lemaitre RN|
|Journal||Am J Clin Nutr|
|Date Published||2016 Feb|
|Keywords||Apolipoproteins E, ATP Binding Cassette Transporter 1, Cholesterol, HDL, Cohort Studies, Diet, DNA Methylation, Eicosapentaenoic Acid, Epigenesis, Genetic, Fatty Acids, Gene Expression Regulation, Humans, Lipids, Polymorphism, Single Nucleotide, Promoter Regions, Genetic, Triglycerides|
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.
|Alternate Journal||Am J Clin Nutr|
|PubMed Central ID||PMC5260796|
|Grant List||R01 HL104135 / HL / NHLBI NIH HHS / United States |
5RC2HL102419 / HL / NHLBI NIH HHS / United States
R01 HL120393 / HL / NHLBI NIH HHS / United States
T32NS054584 / NS / NINDS NIH HHS / United States
HL111089 / HL / NHLBI NIH HHS / United States
UL1 TR000124 / TR / NCATS NIH HHS / United States
R01 HL105756 / HL / NHLBI NIH HHS / United States
1R01HL101250-01 / HL / NHLBI NIH HHS / United States
P30 DK063491 / DK / NIDDK NIH HHS / United States
U01 HL072524 / HL / NHLBI NIH HHS / United States
HL116747 / HL / NHLBI NIH HHS / United States
UM1 CA182913 / CA / NCI NIH HHS / United States
5R01HL1043135-04 / HL / NHLBI NIH HHS / United States
U01HL072524-04 / HL / NHLBI NIH HHS / United States
HL092111 / HL / NHLBI NIH HHS / United States
K08 HL112845 / HL / NHLBI NIH HHS / United States
R01 HL111089 / HL / NHLBI NIH HHS / United States
R01 HL116747 / HL / NHLBI NIH HHS / United States
R01 HL092111 / HL / NHLBI NIH HHS / United States