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

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Lillycrop, KA, Garratt, ES, Titcombe, P, Melton, PE ORCID: 0000-0003-4026-2964, Murray, RJS, Barton, SJ, Clarke-Harris, R, Costello, PM, Holbrook, JD, Hopkins, JC, Childs, CE, Paras-Chavez, C, Calder, PC, Mori, TA, Beilin, L, Burdge, GC, Gluckman, PD, Inskip, HM, Harvey, NC, Hanson, MA, Huang, R-C, Cooper, C and Godfrey, KM 2019 , 'Differential SLC6A4 methylation: a predictive epigenetic marker of adiposity from birth to adulthood' , International Journal of Obesity, vol. 43, no. 5 , pp. 974-988 , doi: 10.1038/s41366-018-0254-3.

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Abstract

Background The early life environment may influence susceptibility to obesity and metabolic disease in later life throughepigenetic 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 wasmeasured by pyrosequencing. We measured DNA methylation in umbilical cord (UC) from children in the SouthamptonWomen’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 wasperformed 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 withhigher triceps skinfold thickness at birth (p = 0.013), 6 months (p = 0.038), 12 months (p = 0.062), 2 years (p = 0.0003), 3years (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 ofadiposity across the life course.

Item Type: Article
Authors/Creators: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
Keywords: DNA methylation, Raine Study, adiposity, SLC6A4, obesity
Journal or Publication Title: International Journal of Obesity
Publisher: Nature Publishing Group
ISSN: 0307-0565
DOI / ID Number: 10.1038/s41366-018-0254-3
Copyright Information:

© 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 thesource, provide a link to the Creative Commons license, and indicate if changes were made.

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