Department of Nutrition and Food Hygiene, College of Public Health, Harbin Medical University, Harbin, Heilongjiang Province 150081, P. R. China.
The First Psychiatric Hospital of Harbin, Harbin, Heilongjiang Province 150081, P. R. China.
Aging (Albany NY). 2020 Jun 18;12(12):12206-12221. doi: 10.18632/aging.103397.
Prenatal malnutrition could promote renal dysfunction in adulthood, but it is unclear whether the detrimental effect could be transmitted to the next generation. We investigated whether famine exposure was associated with variation of estimated glomerular filtration rate(eGFR) in two generations and explored the mediation role of methylation alterations. The longitudinal analysis included 2909 participants from Suihua rural area. F1 and F2 generations were divided into non-famine and famine group based on their birth year and exposure status of their parents, respectively. The eGFR was calculated by using the chronic kidney disease epidemiology collaboration equation. We applied mixed-effect models to investigate the association between famine and ΔeGFR and tested blood DNA methylomes in 46 families across two generations. The mediation-analysis models were utilized to examine the mediation effect of methylation alterations on the famine-ΔeGFR association.In mixed-effect models, famine exposure was associated with declined ΔeGFR level in F1(β:-8.32;95%CI:-11.51,-5.12) and in F2(β:-6.11;95%CI:-11.88, -0.43). Methylation850K BeadChip data showed only 19 of 961 F1 differentially methylated sites showed concordant alterations in F2. The mediation-analysis results showed methylation alterations on AGTR1 and PRKCA might mediate the famine-ΔeGFR association. Overall, prenatal famine exposure may have long-term effects on eGFR decline across consecutive generations which might be partly mediated by methylation alterations on AGTR1 and PRKCA.
产前营养不良可能会导致成年后肾功能障碍，但目前尚不清楚这种不利影响是否会传递给下一代。我们研究了饥荒暴露是否与两代人的估算肾小球滤过率(eGFR)变化有关，并探讨了甲基化改变的中介作用。这项纵向分析包括来自绥化农村地区的 2909 名参与者。根据父母的出生年份和暴露情况，将 F1 和 F2 代分为非饥荒组和饥荒组。eGFR 通过慢性肾脏病流行病学合作方程计算。我们应用混合效应模型来研究饥荒与ΔeGFR 之间的关系，并在两代人之间的 46 个家庭中检测血液 DNA 甲基组。采用中介分析模型来检验甲基化改变对饥荒-ΔeGFR 关联的中介效应。在混合效应模型中，饥荒暴露与 F1 代 eGFR 下降有关(β：-8.32；95%CI：-11.51，-5.12)和 F2 代 eGFR 下降有关(β：-6.11；95%CI：-11.88，-0.43)。Methylation850K BeadChip 数据显示，961 个 F1 差异甲基化位点中只有 19 个在 F2 中显示出一致的改变。中介分析结果表明，AGTR1 和 PRKCA 上的甲基化改变可能介导了饥荒-ΔeGFR 之间的关联。总的来说，产前饥荒暴露可能对连续几代人的 eGFR 下降有长期影响，这种影响可能部分是由 AGTR1 和 PRKCA 上的甲基化改变介导的。
