产前应激、炎症相关基因的甲基化与儿童早期肥胖指标：肥胖、生长环境与社会应激队列研究计划。
Prenatal Stress, Methylation in Inflammation-Related Genes, and Adiposity Measures in Early Childhood: the Programming Research in Obesity, Growth Environment and Social Stress Cohort Study.
机构信息
From the Department of Occupational and Environmental Health Sciences (Wu), School of Public Health, Peking University, Beijing, China; Population Health and Science Policy (Gennings), Mount Sinai Hospital, New York, New York; Department of Pediatrics (R.J. Wright), Kravis Children's Hospital, The Mindich Child Health & Development Institute (R.J. Wright), and Department of Preventive Medicine, Icahn School of Medicine at Mount Sinai (Just, Svensson, R.O. Wright), New York, New York; Department of Statistics (Wilson), Colorado State University, Fort Collins, Colorado; Department of Neonatology and Obstetrics, Gynecology and Reproductive Biology (Burris), Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts; Department of Epidemiology (Braun), School of Public Health, Brown University, Providence, Rhode Island; Department of Environmental Health Sciences (Zhong, Brennan, Dereix, Baccarelli), Mailman School of Public Health, Columbia University, New York, New York; Center for Research in Nutrition and Health (Cantoral, Téllez-Rojo), National Institute of Public Health, Cuernavaca, Morelos, Mexico; and Division of Research on Community Interventions (Schnaas), National Institute of Perinatology, Mexico City, Mexico.
出版信息
Psychosom Med. 2018 Jan;80(1):34-41. doi: 10.1097/PSY.0000000000000517.
OBJECTIVE
Maternal stress during pregnancy may influence childhood growth and adiposity, possibly through immune/inflammatory programming. We investigated whether exposure to prenatal stress and methylation in inflammation-related genes were associated with childhood adiposity in 424 mother-child pairs in Mexico City, Mexico.
METHODS
A stress index was created based on four prenatally administered stress-related scales (Exposure to Violence, Crisis in Family Systems, State-Trait Anxiety Inventory, and Edinburgh Postnatal Depression Scale). We measured weight, height, body fat mass (BFM), percentage body fat (PBF), and waist circumference in early childhood (age range, 4-6 years). Body mass index (BMI) z scores were calculated according to World Health Organization standards. DNA methylation in gene promoters of tumor necrosis factor α, interleukin 8, and interleukin 6 (IL6) in umbilical cord blood were determined by pyrosequencing.
RESULTS
An interquartile range increase in stress index (27.3) was associated with decreases of 0.14 unit in BMI z score (95% confidence interval [CI] = -0.28 to -0.005), 5.6% in BFM (95% CI = -9.7 to -1.4), 3.5% in PBF (95% CI = -6.3 to -0.5), and 1.2% in waist circumference (95% CI = -2.4 to -0.04) in multivariable-adjusted models. An interquartile range increase in IL6 methylation (3.9%) was associated with increases of 0.23 unit in BMI z score (95% CI = 0.06-0.40), 8.1% (95% CI = 2.3-14.3) in BFM, 5.5% (95% CI = 1.7-9.5) in PBF, and 1.7% (95% CI = 0.2-3.3) in waist circumference.
CONCLUSIONS
Prenatal stress was associated with decreased childhood adiposity, whereas cord blood IL6 methylation was associated with increased childhood adiposity in Mexican children.
目的
孕妇在怀孕期间所承受的压力可能会通过免疫/炎症编程影响儿童的生长和肥胖，我们调查了在墨西哥城的 424 对母婴中，产前压力暴露和炎症相关基因的甲基化是否与儿童肥胖有关。
方法
基于四个产前应激相关量表（暴露于暴力、家庭系统危机、状态特质焦虑量表和爱丁堡产后抑郁量表），我们创建了一个压力指数。我们在儿童早期（年龄范围 4-6 岁）测量体重、身高、体脂肪量（BFM）、体脂肪百分比（PBF）和腰围。根据世界卫生组织的标准计算体重指数（BMI）z 评分。通过焦磷酸测序测定脐带血中肿瘤坏死因子 α、白细胞介素 8 和白细胞介素 6（IL6）基因启动子的 DNA 甲基化。
结果
压力指数的四分位间距增加（27.3）与 BMI z 评分降低 0.14 个单位（95%置信区间[CI]：-0.28 至-0.005）、BFM 降低 5.6%（95% CI：-9.7 至-1.4）、PBF 降低 3.5%（95% CI：-6.3 至-0.5）和腰围增加 1.2%（95% CI：-2.4 至-0.04）有关，在多变量调整模型中。IL6 甲基化的四分位间距增加（3.9%）与 BMI z 评分增加 0.23 个单位（95% CI：0.06-0.40）、BFM 增加 8.1%（95% CI：2.3-14.3）、PBF 增加 5.5%（95% CI：1.7-9.5）和腰围增加 1.7%（95% CI：0.2-3.3）有关。
结论
产前压力与儿童肥胖呈负相关，而脐带血中 IL6 甲基化与儿童肥胖呈正相关。
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