Early-Life Exposure to the Chinese Famine Is Associated with Higher Methylation Level in the INSR Gene in Later Adulthood.
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ABSTRACT:
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]
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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.
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| S-EPMC8565276 | biostudies-literature
Project description:The aims of this study were to explore whether DNA methylation at INSR and IGF2 mediated the association of prenatal exposure to the Chinese great famine with adulthood waist circumference (WC) and BMI. A total of 235 subjects were selected into the present study from severely affected province and a neighbor province with less severely affected famine in China through multi-stage clustered random sampling. DNA methylation at the INSR and IGF2 gene promoter regions was detected by the Sequenom's MassARRAY system. The "mediation" package of R was used to evaluate the mediation effect of DNA methylation on the association between prenatal exposure to the famine and adult WC and BMI. The results showed that prenatal famine exposure was significantly associated with higher overall methylation level of the INSR gene (d = 3.6%; 95% CI 1.2-6.0; P = 0.027) and larger adulthood WC (d = 2.72 cm; 95% CI 0.20-5.24; P = 0.034). Furthermore, famine significantly increased methylation levels at four CpG sites. Methylation of the CpG7 site mediated 32.0% (95% CI 5.0-100.0%, P = 0.029) of the association between prenatal exposure to the Chinese great famine and adulthood WC. In conclusion, Epigenetic changes to the INSR might mediate the adverse effect of prenatal famine exposure on WC in adulthood.
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| S-EPMC6661887 | biostudies-literature
Project description:BACKGROUND:A healthy diet is important for normal growth and development. Exposure to undernutrition during important developmental periods such as childhood and adolescence can have effects later in life. Inhabitants of the west of the Netherlands were exposed to severe undernutrition during the famine in the last winter of the second World War (1944-1945). OBJECTIVE:We investigated if exposure of women to the Dutch famine during childhood and adolescence was associated with an unhealthy lifestyle later in life. DESIGN:We studied 7,525 women from the Prospect-EPIC cohort, recruited in 1993-97 and aged 0-18 years during the Dutch famine. An individual famine score was calculated based on self-reported information about experience of hunger and weight loss. We investigated the association between famine exposure in early life and four lifestyle factors in adulthood: smoking, alcohol consumption, physical activity level and a Mediterranean-style diet. RESULTS:Of the 7,525 included women, 46% were unexposed, 38% moderately exposed and 16% severely exposed to the Dutch famine. Moderately and severely exposed women were more often former or current smokers compared to women that did not suffer from the famine: adjusted prevalence ratio 1.10 (95% CI: 1.05; 1.14) and 1.18 (1.12; 1.25), respectively. They also smoked more pack years than unexposed women. Severely exposed women were more often physically inactive than unexposed women, adjusted prevalence ratio 1.32 (1.06; 1.64). Results did not differ between exposure age categories (0-9 and 10-17 years). We found no associations of famine exposure with alcohol consumption and no dose-dependent relations with diet. CONCLUSIONS:Exposure to famine early in female life may be associated with higher prevalence of smoking and physical inactivity later in life, but not with unhealthy diet and alcohol consumption.
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Project description:Global food security is a major driver of population health, and food system collapse may have complex and long-lasting effects on health outcomes. We examined the effect of prenatal exposure to the Great Chinese Famine (1958-1962)-the largest famine in human history-on pulmonary tuberculosis (PTB) across consecutive generations in a major center of ongoing transmission in China. We analyzed >1 million PTB cases diagnosed between 2005 and 2018 in Sichuan Province using age-period-cohort analysis and mixed-effects metaregression to estimate the effect of the famine on PTB risk in the directly affected birth cohort (F1) and their likely offspring (F2). The analysis was repeated on certain sexually transmitted and blood-borne infections (STBBI) to explore potential mechanisms of the intergenerational effects. A substantial burden of active PTB in the exposed F1 cohort and their offspring was attributable to the Great Chinese Famine, with more than 12,000 famine-attributable active PTB cases (>1.23% of all cases reported between 2005 and 2018). An interquartile range increase in famine intensity resulted in a 6.53% (95% confidence interval [CI]: 1.19-12.14%) increase in the ratio of observed to expected incidence rate (incidence rate ratio, IRR) in the absence of famine in F1, and an 8.32% (95% CI: 0.59-16.6%) increase in F2 IRR. Increased risk of STBBI was also observed in F2. Prenatal and early-life exposure to malnutrition may increase the risk of active PTB in the exposed generation and their offspring, with the intergenerational effect potentially due to both within-household transmission and increases in host susceptibility.
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Project description:BackgroundThe fast-growing literature suggests that the Chinese famine of 1959-1961 drives current and future type 2 diabetes (T2D) epidemics in China. This conclusion may be premature, as many Chinese famine studies have major methodological problems. We examine these problems, demonstrate how they bias the study results, and formulate recommendations to improve the quality of future studies.MethodsWe searched English and Chinese databases for studies that examined the relationship between prenatal exposure to the Chinese famine and adult T2D from inception to 8 February 2022. We extracted information on T2D cases and study populations of individuals born during the famine (famine births), before the famine (prefamine births), and after the famine (postfamine births). We used random-effects models to compare the odds of T2D in famine births to several control groups, including postfamine births, combined pre- and postfamine births, and prefamine births. We used meta-regressions to examine the impacts of age differences between comparison groups on famine effect estimates and the role of other characteristics, including participant sex, age, and T2D assessments; famine intensity; residence; and publication language. Potential sources of heterogeneity and study quality were also evaluated.ResultsTwenty-three studies met our inclusion criteria. The sample sizes ranged from less than 300 to more than 360,000 participants. All studies defined the famine exposure based on the participants' dates of birth, and 18 studies compared famine births and postfamine births to estimate famine effects on T2D. The famine and postfamine births had an age difference of three years or more in all studies. The estimates of the famine effect varied by the selection of controls. Using postfamine births as controls, the OR for T2D among famine births was 1.50 (95% CI 1.34-1.68); using combined pre- and postfamine births as controls, the OR was 1.12 (95% CI 1.02-1.24); using prefamine births as controls, the OR was 0.89 (95% CI 0.79-1.00). The meta-regressions further showed that the famine effect estimates increased by over 1.05 times with each one-year increase in ignored age differences between famine births and controls. Other newly identified methodological problems included the poorly assessed famine intensity, unsuitable study settings for famine research, and poor confounding adjustment.InterpretationThe current estimates of a positive relationship between prenatal exposure to the Chinese famine and adult T2D are mainly driven by uncontrolled age differences between famine births and postfamine births. Studies with more rigorous methods, including age-balanced controls and robust famine intensity measures, are needed to quantify to what extent the famine exposure is related to current T2D patterns in China.
| S-EPMC9317968 | biostudies-literature
Project description:BackgroundNutritional insult in early life brings adaptive changes in body structure and functioning that could remain throughout the affected individual's life course. The long term impact of early life famine exposure on adulthood anthropometric measurements has been recorded in previous studies. However, the results were contradictory. Hence, we extend this study to examine the impact of famine exposure during early life on adulthood's anthropometry among survivors of the 1983-85 Ethiopian great famine.MethodsA total of 1384 adult men and women survived from 1983 to 85 Ethiopian great famine were included in the study. Famine exposure status was classified into five groups: early life-exposed, prenatal-exposed, postnatal-exposed, adolescence-exposed, and non-exposed based on self-reported age and birthdate of the participants. Prenatal, post-natal, and adolescence exposed groups were considered as early life exposed. Following a standard procedure, anthropometric measurements were taken. A linear regression analysis was used to analyze the impact of famine exposure on adult anthropometric measurements adjusted for all possible covariates. The effect of famine exposure on overweight, general obesity, and abdominal obesity was examined using multinomial and binary logistic regression analysis.ResultCompared to non-exposed groups, adult height was lower by 1.83?cm (??=?-?1.83; 95% CI: -?3.05, -?0.58), 1.35?cm (??=?-?1.35; 95% CI: -?2.56, -?0.14) and 2.07?cm (??=?-?2.07?cm; 95% CI: -?3.31, -?0.80) among early life, prenatal and post-natal exposed groups, respectively. Likewise, famine exposure during early life (??=?0.02; 95% CI: 0.01, 0.03), prenatal (??=?0.03; 95% CI: 0.02, 0.03) and post-natal life (??=?0.02; 95% CI: 0.02, 0.03) was positively associated with increased waist to height ratio. However, none of the above exposures resulted in a significant association with body mass index (P?>?0. 05). Additionally, exposure to famine during early stage of life was not associated with increased risk of overweight, general obesity and abdominal obesity in adults.ConclusionDecreased adult height and increased waist-to-height ratio were associated with early life exposure to famine, particularly prenatal and post-natal exposure. These results therefore underscore the significance of avoiding undernutrition in early life, which tends to be important for achieving once potential adult height and to minimize the increased risk of anthropometric markers of abdominal obesity such as waist to height ratio in later life.
| S-EPMC7792120 | biostudies-literature
Project description:ObjectivesFamine exposure in early life was associated with type 2 diabetes, non-alcoholic fatty liver disease and metabolic syndrome, etc. But evidence in early famine exposure and insulin resistance and beta cell dysfunction were limited. We aimed to investigate whether the association existed between famine exposure in early life and beta cell dysfunction and insulin resistance in adulthood.MethodsIn all, 7912 non-diabetic participants were included in this study, based on SPECT-China study. Participants with fetal or childhood famine exposure (birth year 1949-1962) were exposure group. Insulin resistance was estimated by the homeostasis model assessment index of insulin resistance (HOMA-IR). Beta cell function, represented by insulin secretion, was estimated by the disposition index. The associations of famine exposure with HOMA-IR and disposition index were assessed via linear regression.ResultsIn men, we did not observe a significant association between early life famine exposure and ln(HOMA-IR) in all three models (P?>?0.05 for all). However, in women, early life famine exposure were found to have significant association with ln(HOMA-IR) after adjustments for urbanization, severity of famine exposure, current smoker, waist circumference, hypertension, and dyslipidemia (unstandardized coefficients 0.055, 95% confidence interval 0.021, 0.088, P?=?0.001). Early life famine exposure was observed to be negatively associated with ln(disposition index) after adjustments for the above potential confounders, both in men (model 3: unstandardized coefficients -0.042, 95% confidence interval -0.072,-0.012, P?=?0.006) and women (model 3: unstandardized coefficients -0.033, 95% confidence interval -0.058,-0.009, P?=?0.008).ConclusionsIn conclusion, exposure to famine in fetal- and childhood- life period is associated with beta cell dysfunction in males and females without diabetes, but early life famine exposure was only associated with insulin resistance in non-diabetic females. These results indicate that malnutrition in early life period may offer a modifiable factor for type 2 diabetes development.
| S-EPMC7280514 | biostudies-literature