Global DNA methylation: Nutritional Correlates and Child Growth.

Background: Global DNA methylation is a modifiable epigenetic mechanism associated with adult-onset cardiometabolic diseases. Yet, little is known regarding its relation with obesity and there is limited research in children. This work aimed to identify nutritional and sociodemographic predictors of global DNA methylation, and to investigate its association with development of adiposity in school-age children. Methods: Data from the Multi-Ethnic Study of Atherosclerosis Stress Study were used to examine the associations of methyl-donor/methylation cofactor (folate, vitamin B12, vitamin B6, zinc, methionine) micronutrient intake and plasma homocysteine with two measures of global DNA methylation (LINE-1 and Alu). Data from a representative sample of low- and middle-income children in the Bogotá School Children Cohort were used to identify nutritional (biomarkers of folate, vitamin B12, zinc, vitamin A, iron) and sociodemographic correlates of LINE-1 methylation, and to examine its relation with change in adiposity indicators (body mass index (BMI)-for-age, waist circumference-for-age, and subscapular-to-triceps skinfold thickness ratio-for-age) and linear growth (height-for-age) during 2.5 years of follow-up. Results: Among adults, BMI was positively associated with LINE-1 methylation, and height was positively correlated with Alu methylation; micronutrient intake was not associated with global DNA methylation. In school-age children, higher plasma vitamin A and C-reactive protein (CRP) levels, and low maternal BMI were each related to lower LINE-1 methylation, whereas high socioeconomic status was associated with higher DNA methylation. Among boys, there were inverse, non-linear associations of global DNA methylation at baseline with annual change in BMI-for-age and skinfold thickness ratio-for-age. Boys in the lowest quartile of DNA methylation experienced greater gains in both indicators than those in the upper three quartiles during follow-up. Additionally, LINE-1 methylation was inversely related to change in waist circumference in a linear manner. LINE-1 methylation was not related to development of adiposity in girls, and there were no associations between DNA methylation and linear growth in either sex. Conclusions: These findings support the role of environmental and nutritional factors in DNA methylation patterns, and contribute to knowledge of biological mechanisms involved in weight gain. Whether modification of DNA methylation profiles through dietary interventions influences body composition deserves further investigation.PhDEpidemiological ScienceUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/97956/1/perngwei_1.pd