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Differential SLC6A4 methylation: a predictive epigenetic marker of adiposity from birth to adulthood

Citation

Lillycrop, KA and Garratt, ES and Titcombe, P and Melton, PE and Murray, RJS and Barton, SJ and Clarke-Harris, R and Costello, PM and Holbrook, JD and Hopkins, JC and Childs, CE and Paras-Chavez, C and Calder, PC and Mori, TA and Beilin, L and Burdge, GC and Gluckman, PD and Inskip, HM and Harvey, NC and Hanson, MA and Huang, R-C and Cooper, C and Godfrey, KM, Differential SLC6A4 methylation: a predictive epigenetic marker of adiposity from birth to adulthood, International Journal of Obesity, 43, (5) pp. 974-988. ISSN 0307-0565 (2019) [Refereed Article]


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© The Author(s) 2019. This article is licensed under a Creative Commons Attribution 4.0 International License, (http://creativecommons.org/licenses/by/4.0/.) which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.

DOI: doi:10.1038/s41366-018-0254-3

Abstract

Background The early life environment may influence susceptibility to obesity and metabolic disease in later life through epigenetic processes. SLC6A4 is an important mediator of serotonin bioavailability, and has a key role in energy balance. We tested the hypothesis that methylation of the SLC6A4 gene predicts adiposity across the life course. Methods DNA methylation at 5 CpGs within the SLC6A4 gene identified from a previous methyl binding domain array was measured by pyrosequencing. We measured DNA methylation in umbilical cord (UC) from children in the Southampton Women’s Survey cohort (n = 680), in peripheral blood from adolescents in the Western Australian Pregnancy Cohort Study (n = 812), and in adipose tissue from lean and obese adults from the UK BIOCLAIMS cohort (n = 81). Real-time PCR was performed to assess whether there were corresponding alterations in gene expression in the adipose tissue. Results Lower UC methylation of CpG5 was associated with higher total fat mass at 4 years (p = 0.031), total fat mass at 6– 7 years (p = 0.0001) and % fat mass at 6–7 years (p = 0.004). Lower UC methylation of CpG5 was also associated with higher triceps skinfold thickness at birth (p = 0.013), 6 months (p = 0.038), 12 months (p = 0.062), 2 years (p = 0.0003), 3 years (p = 0.00004) and 6–7 years (p = 0.013). Higher maternal pregnancy weight gain (p = 0.046) and lower parity (p = 0.029) were both associated with lower SLC6A4 CpG5 methylation. In adolescents, lower methylation of CpG5 in peripheral blood was associated with greater concurrent measures of adiposity including BMI (p ≤ 0.001), waist circumference (p = 0.011), subcutaneous fat (p ≤ 0.001) and subscapular, abdominal and suprailiac skinfold thicknesses (p = 0.002, p = 0.008, p = 0.004, respectively). In adipose tissue, methylation of both SLC6A4 CpG5 (p = 0.019) and expression of SLC6A4 (p = 0.008) was lower in obese compared with lean adults. Conclusions These data suggest that altered methylation of CpG loci within SLC6A4 may provide a robust marker of adiposity across the life course.

Item Details

Item Type:Refereed Article
Keywords:DNA methylation, Raine Study, adiposity, SLC6A4, obesity
Research Division:Biological Sciences
Research Group:Genetics
Research Field:Epigenetics (incl. genome methylation and epigenomics)
Objective Division:Health
Objective Group:Specific population health (excl. Indigenous health)
Objective Field:Neonatal and child health
UTAS Author:Melton, PE (Dr Phillip Melton)
ID Code:144256
Year Published:2019
Web of Science® Times Cited:6
Deposited By:Menzies Institute for Medical Research
Deposited On:2021-05-04
Last Modified:2021-06-02
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