Abstract
We examined the association between the China famine exposure in early life and DNA methylation of INSR (hg18, chr19:7110130-7110574) and CPT1A (hg18, chr11: 68286513-68286952) related to growth and metabolism in 235 subjects selected from two provinces in China. The subjects were categorized into prenatal famine-exposed group and non-exposed group based on their birthdates. DNA methylation at the INSR gene locus was assayed from peripheral white blood cells using the Sequenom’s MassARRAY system. Two dependent samples t-test was used to compare the difference between the exposed group and non-exposed group. DNA methylation level of INSR was higher among individuals who exposed to the China famine in the fetus than that of non-exposed group (d = 3.3%, P = 0.006). A significant interaction between famine exposure and province was observed for INSR (Pinteraction < 0.001). DNA methylation level of INSR was positively associated with triglyceride (β = 0.011, P = 0.021), and negatively associated with high-density lipoprotein cholesterol (β = −0.039, P = 0.021). Moreover, exposed group had higher meat consumption than non-exposed group in severe exposure area. Prenatal exposure to the China famine plus later life eating habits might regulate epigenome.
Highlights
The altered DNA methylation of genes related to growth and metabolic may play an important role in leading to such effect
A genome-scale analysis identified prenatal malnutrition-associated different methylation regions (P-differential methylation regions (DMRs)) in the Dutch study and observed that DNA methylation level in the intragenic enhancer regions of INSR and CPT1A were associated with both prenatal famine exposure and serum low-density lipoprotein cholesterol[19]
We found that only severe famine exposure had higher levels of the WC and Fasting plasma glucose (FPG) and higher frequency of alcohol use than non-exposed group (P < 0.05)
Summary
The altered DNA methylation of genes related to growth and metabolic may play an important role in leading to such effect. Decrease the DNA methylation level in promoters regions of the glucocorticoid receptor (GR) and peroxisomal proliferator-activated receptor (PPAR) genes in rat offspring, and leads to persistent phenotypes changes[15], which could be transmitted even to the generation[16,17,18] These patterns were detected in humans according to the studies of the Dutch famine[19,20]. No study has been designed to explore the relationship between prenatal exposure to China famine and alteration of DNA methylation in later years To this end, two common candidate genes related to growth and metabolic, INSR and CPT1A, were selected in the present study and the associations between China famine exposure in fetus and DNA methylation in adulthood were explored
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