Dietary intake, plasma homocysteine, and repetitive element DNA methylation in the Multi-Ethnic Study of Atherosclerosis (MESA).
OBJECTIVE
DNA methylation of repetitive elements may explain the relations between dietary intake, hyperhomocysteinemia, and cardiovascular disease risk. We investigated associations of methyl micronutrient intake and plasma total homocysteine with LINE-1 and Alu methylation in a cross-sectional study of 987 adults aged 45-84 y who participated in the Multi-Ethnic Study of Atherosclerosis (MESA) Stress Study.


RESULTS
DNA methylation was estimated using pyrosequencing technology. A 120-item food frequency questionnaire was used to ascertain daily intake of folate, vitamin B12, vitamin B6, zinc, and methionine. Plasma total homocysteine was quantified using a fluorescence polarization immunoassay. Associations of micronutrient intake and homocysteine with LINE-1 and Alu methylation were examined using linear regression. Adjusted differences in %5-methylated cytosines (%5 mC) were examined by categories of predictors using multivariable linear regression models. Intake of methyl-donor micronutrients was not associated with DNA methylation. After adjustment for covariates, each 3 μmol/L increment of homocysteine corresponded with 0.06 (-0.01, 0.13) %5 mC higher LINE-1 methylation. Additionally, BMI was positively associated with LINE-1 methylation (P trend = 0.03). Participants with BMI ≥ 40 kg/m² had 0.35 (0.03, 0.67) %5 mC higher LINE-1 than those with normal BMI. We also observed a 0.10 (0.02, 0.19) %5 mC difference in Alu methylation per 10 cm of height. These associations did not differ by sex.


CONCLUSIONS
Dietary intake of methyl-donor micronutrients was not associated with measures of DNA methylation in our sample. However, higher BMI was related to higher LINE-1 methylation, and height was positively associated with Alu methylation.
Department of Epidemiology, University of Michigan School of Public Health, Ann Arbor, MI, USA. Electronic address: wei.perng@gmail.com.
W
W
Perng
Department of Epidemiology, University of Michigan School of Public Health, Ann Arbor, MI, USA.
E
E
Villamor
Center for Healthy Communities, Michigan Public Health Institute, Okemos, MI, USA.
M R
MR
Shroff
Division of Epidemiology, Human Genetics, and Environmental Sciences, University of Texas Health Science Center, Houston, TX, USA.
J A
JA
Nettleton
Department of Environmental Health Science, School of Public Health and Health Sciences, University of Massachusetts, Amherst, MA, USA.
J R
JR
Pilsner
Sticht Center on Aging, Wake Forest University, Winston-Salem, NC, USA.
Y
Y
Liu
Department of Epidemiology, University of Michigan School of Public Health, Ann Arbor, MI, USA.
A V
AV
Diez-Roux
D000368:Aged; D000369:Aged, 80 and over; D020087:Alu Elements; D050197:Atherosclerosis / Q000150:complications / Q000453:epidemiology / Q000209:etiology* / Q000378:metabolism; D015415:Biomarkers / Q000097:blood; D001827:Body Height; D015992:Body Mass Index; D003430:Cross-Sectional Studies; D019175:DNA Methylation; D004032:Diet / Q000009:adverse effects*; D005260:Female; D006710:Homocysteine / Q000097:blood*; D006801:Humans; D020138:Hyperhomocysteinemia / Q000150:complications / Q000453:epidemiology / Q000209:etiology* / Q000378:metabolism; D020084:Long Interspersed Nucleotide Elements; D015141:Los Angeles / Q000453:epidemiology; D008297:Male; D018977:Micronutrients / Q000172:deficiency / Q000378:metabolism; D008875:Middle Aged; D009519:New York City / Q000453:epidemiology; D009767:Obesity, Morbid / Q000150:complications; D012307:Risk Factors
D015415:Biomarkers; D018977:Micronutrients; D006710:Homocysteine
Alu; Cardiovascular disease; DNA methylation; Height; Homocysteine; LINE-1; Obesity