Dataset Information

Early-Life Exposure to the Chinese Famine Is Associated with Higher Methylation Level in the INSR Gene in Later Adulthood.

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?

SUBMITTER: Wang Z

PROVIDER: S-EPMC6399294 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature

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Early-Life Exposure to the Chinese Famine Is Associated with Higher Methylation Level in the INSR Gene in Later Adulthood.

Wang Zhenghe Z Song Jieyun J Li Yanhui Y Dong Bin B Zou Zhiyong Z Ma Jun J

Scientific reports 20190304 1

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 ...[more]

PMID: 30833584

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Project description:ObjectiveTo evaluate the association of early-life exposure to the Chinese Great Famine (1959-1961) with DNA methylation in IGF2 and its subsequent influence on blood lipid levels in late adulthood among participants of the Genomic Research of the Chinese Famine (GRECF) study.MethodsThe GRECF study recruited 790 participants born between 1956 and 1964 from 2 neighbor provinces, Anhui and Jiangxi, in China through a multistage, clustered, random sampling. The current study included a random sample of 188 GRECF participants. IGF2 differential methylation region (DMR) is an intragenic DMR located upstream of the imprinted promoters of IGF2 exon 3. DNA methylation were quantified at 8 cytosine-phosphate-guanine dinucleotides (CpG) sites at the IGF2 DMR (chr11p15.5) using the Sequenom EpiTYPER method and the MassARRAY system. Multivariate linear regressions were used to evaluate pairwise associations among famine severity, DNA methylation in the IGF2 gene, and lipid levels. We controlled for age and sex in the base model and additionally controlled for education, smoking, and drinking status 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 lipid levels.ResultsExposure to severe famine was associated with elevated methylation at CpG1 (chr11: 2126041, build 36) of the IGF2 DMR (β = 0.07; P = 0.0008) and total cholesterol (β = 0.72; P = 1.09 × 10-7). After adjustment for age and sex, each unit increase in methylation of the CpG1 site was associated with 1.09-unit increase in total cholesterol (P = 0.03). After further adjustment for all covariates, these associations were still significant (Pfamine-CpG1 = 0.002, Pfamine-total cholesterol = 1.28 × 10-6, and PCpG1-total cholesterol = 0.05).ConclusionIncreased methylation level in the IGF2 gene was associated with early-life exposure to severe famine, and this change was also positively associated with total cholesterol in late adulthood.

Project description:In the past decade, in low-income countries, there have been a rapid rise in prevalence of diabetes among adult population. Hence, understanding the context specific drivers of this change including the impacts of childhood nutrition adversaries on adult metabolic conditions is critical undertaking. This study investigates the potential effects of prenatal famine exposure to the Ethiopian great famine (1983-1985) on adulthood blood glucose level of survivors. A total of 441 adults (222 exposed and 219 controls) were included in the study. Self-reported place of birth and, date of birth and/or age were used to identify participants. A multivariable linear regression analysis was used to analyze the impact of prenatal famine exposure on the level of fasting blood glucose. In linear regression, unadjusted model (Model 1), fasting blood glucose level was increased by 4.13 (β = 4.13; 95% CI .41, 7.42) points in prenatal famine exposed groups, compared with non-exposed. Similarly, the positive association of prenatal famine exposure and fasting blood glucose level was maintained after adjusted for sex (Model 2) (β = . 4.08 95% CI .056, 7.50). Further adjusted for age, residence, educational status, wealth index and family size (Model 3) resulted in 4.10 (β = . 4.10 95% CI .45, 7.56) points increases in fasting blood glucose level. In model 4 adjusting for dietary pattern, physical activity level and family history of diabetes, alcohol and cigarette smoking resulted in 3.90 (β = 3.90, 95% CI 039, 7.52) points increase in fasting glucose level. In the he full adjusted model (Model 5) prenatal exposure to famine was resulted in 3.78 (β = 3.78, 95% CI .22, 7.34) increases in fasting blood glucose level after adjusted for BMI and waist to height ratio. There existed a positive association of prenatal famine exposure and adulthood blood glucose levels. In this population, establishing effective overweight/obesity prevention programs to minimize the co-impact of early famine exposure on blood glucose control are important.

Project description:ObjectivesIntrauterine malnutrition has a long-term effect on respiratory and lung function. However, few studies have explored the association between early-life exposure to famine with asthma and chronic obstructive pulmonary disease (COPD) in adulthood. Therefore, we aimed to investigate the association of early-life exposure to the Chinese famine of 1959-1962 with asthma and COPD later in life.MethodsThis national population-based study included 6,771 participants from the baseline survey of the China Health and Retirement Longitudinal Study (CHARLS) who were born around the time of the Chinese famine. The famine exposure groups were determined according to the participants' birth year as non-exposed (1964-1967), fetal-exposed (1959-1962), preschool-exposed (1954-1957), and school-age exposed (1950-1953). Information about the demographic characteristics, self-reported doctor-diagnosed asthma and COPD, behavior and lifestyles, and indoor pollution were collected using validated questionnaires. In addition, peak expiratory flow (PEF) was measured to assess pulmonary function. Multivariable logistic regression and generalized linear mixed models were performed to explore the risk of adult asthma and COPD, PEF changes during various famine exposure periods compared with the non-exposed group. Stratified and sensitivity analyses were conducted to examine the modification and robustness of the association.ResultsThe prevalence of doctor-diagnosed asthma and COPD was 2.8 and 8.1%, respectively. Compared with the non-exposed group, the risk was significantly higher in the fetal-exposed group for asthma [adjusted odds ratio, (aOR) = 1.87, 95% confidence interval (CI):1.14-3.07] and the school-age exposed group [1.30 (1.00-1.69)] for COPD after controlling for confounders. Furthermore, we observed that fetal exposure to famine was significantly associated with a decrement of PEF in adulthood [β = -11.38 (-22.75 to -0.02)] compared with the non-exposed group. Stratified analyses showed that the association of asthma was stronger in men, who resided in severely famine-affected areas, smoked, and used solid fuels for cooking. No clearly consistent association was observed for subsequent COPD.ConclusionsOur results suggest that fetal exposure to the Chinese famine is significantly associated with the increased risk of asthma in adulthood. Future prospective studies are warranted to examine the association and mechanisms.

Dataset Information

Early-Life Exposure to the Chinese Famine Is Associated with Higher Methylation Level in the INSR Gene in Later Adulthood.

Publications

Early-Life Exposure to the Chinese Famine Is Associated with Higher Methylation Level in the INSR Gene in Later Adulthood.

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