PNAS：母亲的胃肠分流手术与子女的心脏健康有联系

日前，一项最新研究发现，与母亲接受胃肠分流手术之前生下的子女相比，在母亲接受胃肠分流手术之后生下的子女身上观察到的心血管健康标记的改善可能源于基因甲基化的差异。

此前的研究已经发现为了减肥而接受了胃肠分流手术的母亲在手术之后生下的子女比她们在接受手术之前生下的子女的肥胖发生率更低、肥胖程度更低、更少患有高血压，而且他们有更高的胰岛素敏感性。

为了检验这种手术对后代的心脏健康遗传标记的作用，研究人员招募了在魁北克市及其周边居住的20名没有亲缘关系的35到51岁的母亲，她们曾接受过一种被称为胆胰旷置术联合十二指肠转位术的胃肠分流手术，目的是治疗严重的肥胖症。

研究人员对两个各包含25名后代的群组进行了基因表达分析，其中一个群组成员出生于母亲接受该手术之前，而另一个群组成员则出生于母亲接受该手术之后;这些后代的年龄从2岁到25岁不等。

研究人员发现这两个组的5698个基因——特别是那些参与炎症、血管疾病和葡萄糖代谢控制的基因——其甲基化的方式不同;甲基化是一种已知会影响基因表达的化学修饰。

此外，研究人员观察到了基因甲基化水平和与心血管疾病和糖尿病有关的基因功能之间的相关性，这提示了此前报道的在母亲接受胃肠分流手术之后出生的后代的代谢改善背后的潜在机制。

这些发现提示了在母亲手术干预、子宫环境变化与后代基因表达之间的联系。

Differential methylation in glucoregulatory genes of offspring born before vs. after maternal gastrointestinal bypass surgery
Abstract
Obesity and overnutrition during pregnancy affect fetal programming of adult disease. Children born after maternal bariatric gastrointestinal bypass surgery (AMS) are less obese and exhibit improved cardiometabolic risk profiles carried into adulthood compared with siblings born before maternal surgery (BMS). This study was designed to analyze the impact of maternal weight loss surgery on methylation levels of genes involved in cardiometabolic pathways in BMS and AMS offspring. Differential methylation analysis between a sibling cohort of 25 BMS and 25 AMS (2–25 y-old) offspring from 20 mothers was conducted to identify biological functions and pathways potentially involved in the improved cardiometabolic profile found in AMS compared with BMS offspring. Links between gene methylation and expression levels were assessed by correlating genomic findings with plasma markers of insulin resistance (fasting insulin and homeostatic model of insulin resistance). A total of 5,698 genes were differentially methylated between BMS and AMS siblings, exhibiting a preponderance of glucoregulatory, inflammatory, and vascular disease genes. Statistically significant correlations between gene methylation levels and gene expression and plasma markers of insulin resistance were consistent with metabolic improvements in AMS offspring, reflected in genes involved in diabetes-related cardiometabolic pathways. This unique clinical study demonstrates that effective treatment of a maternal phenotype is durably detectable in the methylome and transcriptome of subsequent offspring.