Is famine exposure during developmental life in rural Bangladesh associated with a metabolic and epigenetic signature in young adulthood? A historical cohort study.
Is famine exposure during developmental life in rural Bangladesh associated with a metabolic and epigenetic signature in young adulthood? A historical cohort study.
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DOI：
10.1136/bmjopen-2016-011768
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发表时间：
2016-11-23
期刊：
影响因子：
2.9
通讯作者：
Hitman GA
中科院分区：
文献类型：
--
作者：
Finer S;Iqbal MS;Lowe R;Ogunkolade BW;Pervin S;Mathews C;Smart M;Alam DS;Hitman GA
子宫内的饥饿暴露可以“编程”一个人在以后的生活中患上2型糖尿病和肥胖症。我们试图确定，（1）在发育过程中暴露于饥荒的孟加拉国人是否被编程为糖尿病和肥胖症，（2）这种编程是否特定于妊娠期或出生后的暴露窗口，以及（3）表观遗传差异是否与饥荒暴露有关。作为更广泛的横断面调查的一部分，进行了历史队列研究。通过出生日期和历史记录定义饥荒暴露，并根据以下条件选择参与者：（A）出生后生活中的饥荒暴露，（B）妊娠期间的饥荒暴露和（C）未暴露。孟加拉国吉大港省的一个农村地区。招募年轻成年男性和女性（n=190）参加历史队列研究，随机子样本纳入表观遗传学研究（n=143）。体重、体重指数和口服葡萄糖耐量试验（0和120分钟葡萄糖）的主要结局指标。 次要结果指标包括使用全基因组DNA甲基化和对母体营养敏感的亚稳态表观等位基因的靶向分析。更多的年轻成年人暴露于饥饿在妊娠期体重不足比那些出生后暴露或未暴露。相比之下，与妊娠期暴露或未暴露的年轻人相比，产后暴露于饥荒的年轻人超重的人数更多。在妊娠期宫内暴露于饥饿的体重不足的成年人在葡萄糖耐量试验后出现高血糖，与未暴露的人相比，出生后暴露的人空腹血糖升高。鉴定了已知随妊娠饥饿暴露而变化的7个亚稳态表观等位基因（VTRNA 2 -1、PAX 8、PRDM-9、接近ZFP 57、接近BOLA、EXD 3）的DNA甲基化的显著差异。饥饿暴露在发展的生活编程孟加拉国后代对糖尿病和肥胖症在成年期，但妊娠期和出生后的窗口暴露的表型有不同的影响。DNA甲基化差异复制在以前确定的亚稳态表观等位基因敏感的围概念饥饿曝光。
Famine exposure in utero can ‘programme’ an individual towards type 2 diabetes and obesity in later life. We sought to identify, (1) whether Bangladeshis exposed to famine during developmental life are programmed towards diabetes and obesity, (2) whether this programming was specific to gestational or postnatal exposure windows and (3) whether epigenetic differences were associated with famine exposure. A historical cohort study was performed as part of a wider cross-sectional survey. Exposure to famine was defined through birth date and historical records and participants were selected according to: (A) exposure to famine in postnatal life, (B) exposure to famine during gestation and (C) unexposed. Matlab, a rural area in the Chittagong division of Bangladesh. Young adult men and women (n=190) recruited to a historical cohort study with a randomised subsample included in an epigenetic study (n=143). Primary outcome measures of weight, body mass index and oral glucose tolerance tests (0 and 120 min glucose). Secondary outcome measures included DNA methylation using genome-wide and targeted analysis of metastable epialleles sensitive to maternal nutrition. More young adults exposed to famine in gestation were underweight than those postnatally exposed or unexposed. In contrast, more young adults exposed to famine postnatally were overweight compared to those gestationally exposed or unexposed. Underweight adults exposed to famine in gestation in utero were hyperglycaemic following a glucose tolerance test, and those exposed postnatally had elevated fasting glucose, compared to those unexposed. Significant differences in DNA methylation at seven metastable epialleles (VTRNA2-1, PAX8, PRDM-9, near ZFP57, near BOLA, EXD3) known to vary with gestational famine exposure were identified. Famine exposure in developmental life programmed Bangladeshi offspring towards diabetes and obesity in adulthood but gestational and postnatal windows of exposure had variable effects on phenotype. DNA methylation differences were replicated at previously identified metastable epialleles sensitive to periconceptual famine exposure.
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