Journal
AGING-US
Volume 12, Issue 12, Pages 12206-12221Publisher
IMPACT JOURNALS LLC
DOI: 10.18632/aging.103397
Keywords
prenatal; famine exposure; transgenerational; DNA methylation
Categories
Funding
- National Natural Science Foundation of China [81803227]
- Young Elite Scientists Sponsorship Program by CAST [2019QNRC001]
- National Key R&D Program of China [2017YFC1307401]
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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.eGFR 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-Delta eGFR association. In mixed-effect models, famine exposure was associated with declined.eGFR level in F1 (beta:-8.32;95%CI:-11.51,5.12) and in F2 (beta:-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-Delta eGFR association. Overall, prenatal famDine exposure may have long-term effects on eGFR decline across consecutive generations which might be partly mediated by methylation alterations on AGTR1 and PRKCA.
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