Research Paper Volume 12, Issue 12 pp 12206—12221
Prenatal famine exposure and estimated glomerular filtration rate across consecutive generations: association and epigenetic mediation in a population-based cohort study in Suihua China
- 1 Department of Nutrition and Food Hygiene, College of Public Health, Harbin Medical University, Harbin, Heilongjiang Province 150081, P. R. China
- 2 The First Psychiatric Hospital of Harbin, Harbin, Heilongjiang Province 150081, P. R. China
Received: January 8, 2020 Accepted: May 25, 2020 Published: June 18, 2020https://doi.org/10.18632/aging.103397
How to Cite
Copyright © 2020 Jiang et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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.
eGFR: estimated glomerular filtration rate; AGTR1: angiotensin II receptor 1; PRKCA: protein kinase C alpha; T2D: type 2 diabetes; CKD: chronic kidney disease; FFQ: food-frequency questionnaire; FPG: fast plasma glucose; 2-hPG: 2-hour postprandial glucose; BUN: blood urea nitrogen; UA: uric acid; CRE: serum creatinine; SBP: systolic blood pressure; DBP: diastolic blood pressure; CKD-EPI: chronic kidney disease epidemiology collaboration; BMI: body mass index; SNP: single nucleotide polymorphism; DNA: deoxyribonucleic acid; BMIQ: beta mixture quantile normalization method; FDR: false discovery rate; CpG: cytosine-phosphoric acid-guanine; PCR: polymerase chain reaction; TSS: transcriptional start site; DMSs: differentially methylated sites; CUX1: Homeobox protein cut-like 1; PPARGC1A: peroxisome proliferator-activated receptor gamma coactivator 1-alpha; ELMO1: Engulfment and cell motility protein 1; R^2*: the proportion of residual variance; R^2~: the proportion of original variance; SLC38A2: solute carrier family 38 member 2; PPAP2C: phospholipid phosphatase 2; ZNF385A: zinc finger protein 385A; FAM150B: family with sequence similarity 150 member B..