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. 2019 Jul;98(28):e16424.
doi: 10.1097/MD.0000000000016424.

MC4R and HNF4α promoter methylation at birth contribute to triglyceride levels in childhood: A prospective cohort study

Eun Jin Kwon  1 , Hye Ah Lee  2 , Young-Ah You  1 , Jae Young Yoo  1 , Hyesook Park  3 , Eun Ae Park  4 , Eun Hee Ha  5 , Young Ju Kim  6
Affiliations

MC4R and HNF4α promoter methylation at birth contribute to triglyceride levels in childhood: A prospective cohort study

Eun Jin Kwon et al. Medicine (Baltimore). 2019 Jul.

Abstract

Although the changes in DNA methylation are assumed to be due to the association between adverse intrauterine conditions and adult metabolic health, evidence from human studies is rare. Little is known about the changes in DNA methylation present at birth that affect metabolic profiles in childhood. Previous studies have shown that the melanocortin 4 receptor (MC4R) and hepatocyte nuclear factor 4 alpha (HNF4α) genes are associated with obesity and metabolic disorders. Thus, we investigated the associations of the DNA methylation statuses of MC4R and HNF4α in cord blood with metabolic profiles in childhood.We collected data from 90 children 7 to 9 years of age included in the Ewha Birth & Growth Cohort Study in Korea. DNA methylation was analyzed by pyrosequencing. The children were split into 2 groups according to the cutoff triglyceride (TG) levels (<110 and ≥110 mg/dL).The methylation statuses of MC4R and HNF4α at birth were significantly associated with the TG level in childhood (P < .05). It was interesting to note that the methylation statuses of MC4R and HNF4α in cord blood were significantly decreased, whereas childhood body mass index was significantly increased, in children with high TG levels compared with children with low TG levels (P < .05).Our findings show that the methylation statuses of MC4R and HNF4α at birth are associated with metabolic profiles in childhood. These epigenetic modifications occurring in early life may contribute to subsequent metabolic-related disorders. Thus, we suggest that DNA methylation status in cord blood may be predictive of the risk of developing metabolic syndrome.

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Conflict of interest statement

The authors have no conflicts of interest to disclose.

Figures

Figure 1
Figure 1
Analysis of the associations between triglyceride (TG) levels and the methylation statuses of the melanocortin 4 receptor (MC4R) and hepatocyte nuclear factor 4 alpha (HNF4a) promoters in the blood of children, after adjustment for sex, child's age, and child's body mass index.
Figure 2
Figure 2
DNA methylation statuses of melanocortin 4 receptor (MC4R) and hepatocyte nuclear factor 4 alpha (HNF4α) at CpG sites in cord blood and child's body mass index (BMI) according to triglyceride (TG) levels in children. (A) P-values were calculated by analysis of covariance (ANCOVA), adjusting for maternal age, prepregnancy BMI, mother's education, gestational age (GA), sex, birth weight, child's age, child's BMI, and DNA methylation levels in children. (B) P-values were calculated by ANCOVA, adjusting for maternal age, prepregnancy BMI, mother's education, GA, sex, birth weight, child's age, and DNA methylation levels in cord blood. Dotted lines (----) represent differences in the methylation status between low TG and high TG levels. Solid lines (—) represent differences in BMI in childhood between low and high TG levels.
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