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Abstract

Background: To examine methylation of the peroxisome proliferator-activated receptor. (PPAR gamma) gene and its relationship with child weight status, at birth and 9 years.Methods: We measured PPAR gamma methylation across 23 CpG sites using the Infinium Illumina 450 k array for children from the Center for the Health Assessment of Mothers and Children of Salinas (CHAMACOS) cohort at birth (N = 373) and 9 years (N = 245).Results: Methylation level correlation patterns across the 23 PPAR gamma CpG sites were conserved between birth and 9-year ages. We found high inter-CpG correlations between sites 1-3 (methylation block 1) and also between sites 18-23 (methylation block 2) for both time points, although these patterns were less pronounced at 9 years. Additionally, sites 1-3 (north shore) had the highest intra-CpG correlations over time (r = 0.24, 0.42, and 0.3; P = 0.002, P < 0.001, P < 0.001, respectively). PPAR gamma methylation levels tended to increase with age, and the largest differences were observed for north shore sites (7.4%). Adjusting for sex, both site 1 and site 20 (gene body) methylation at birth was significantly and inversely associated with birth weight (beta = -0.13, P = 0.033; beta = -0.09, P = 0.025, respectively). Similarly, we found that site 1 and site 20 methylation at 9 years was significantly and inversely associated with 9-year BMI z-score (beta = -0.41, P = 0.015; beta = -0.23, P = 0.045, respectively).Conclusion: Our results indicate that PPAR gamma methylation is highly organized and conserved over time, and highlight the potential functional importance of north shore sites, adding to a better understanding of regional human methylome patterns. Overall, our results suggest that PPAR gamma methylation may be associated with child body size.

Authors

Volberg, Vitaly;  Yousefi, Paul;  Huen, Karen;  Harley, Kim;  Eskenazi, Brenda;  Holland, Nina

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