Abstract P110: Early-Life Exposure to Severe Famine is Associated With Higher Methylation Level in the IGF2 Gene and Higher Total Cholesterol in Late Adulthood: The Genomic Research of the Chinese Great Famine (GRECF) Study

Abstract

Objective: To evaluate association of early-life exposure to the Chinese Great Famine (1959-1961) with DNA methylation in IGF2 , a gene involved in growth and development, and its subsequent influence on blood lipid levels in late adulthood among participants of the Genomic Research of the Chinese Great Famine (GRECF) study. Methods: The GRECF study recruited 790 participants born between 1956 and 1964 from two neighbor provinces, Anhui and Jiangxi, in China through a multistage, clustered, random sampling. Historically, famine was severe in Anhui and moderate in Jiangxi. Besides individuals born in Anhui province, those who were born during or before the Chinese Great Famine in Jiangxi province and reported having siblings starved to death were also categorized as having severe famine exposure; All other participants born in Jiangxi province were considered as having moderate famine exposure. DNA methylation within the IGF2 gene locus were assayed using the Sequenom’s MassARRAY system among a random sample of 188 participants. Total cholesterol (TC), low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol were assayed using enzymatic colormetric tests. Triglycerides was calculated using the Friedman formula and was logarithmically transformed for analyses. Multivariate linear regressions were used to evaluate associations of famine severity with lipids, famine severity with DNA methylation in the IGF2 , and DNA methylation in the IGF2 with lipids, respectively, controlling for sex in the base model and additionally controlling for age, education, smoking, and drinking in the fully adjusted model. Mediation analysis was applied to assess the mediation effect of DNA methylation at the IGF2 gene on the association between early-life exposure to severe famine and adult lipids levels. Results: DNA methylation was quantified at 8 cytosine-phosphate-guanine dinucleotides (CpG) sites in the IGF2 gene. Exposure to severe famine was associated with higher methylation level at one site of the IGF2 gene (CpG1: β =0.07, P =5.00х10 -4 ) and increased levels of TC ( β =0.85; P =9.30х10 -7 ). Furthermore, per unit increase in methylation of the CpG1 site was associated with 1.13-unit increase in TC ( P =0.02). After further adjustment for all covariates, these associations were still significant ( P famine-CpG1 =0.03; P famine-TC =7.55х10 -6 ; P CpG1-TC = 0.05). Methylation of the CpG1 site mediated 6% ( P =0.18) of the association between exposure to the severe Chinese Great Famine and adult TC. Conclusion: Increased methylation level in the IGF2 gene may be a consequence of early-life exposure to severe famine during the Chinese Great Famine and this change was also positively associated with TC in late adulthood.