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

Autor: Lillycrop KA; Centre for Biological Sciences, Faculty of Natural and Environmental Sciences, University of Southampton, Southampton, UK. kal@soton.ac.uk.; NIHR Southampton Biomedical Research Centre, University of Southampton and University Hospital Southampton NHS Foundation Trust, Southampton, UK. kal@soton.ac.uk., Garratt ES; NIHR Southampton Biomedical Research Centre, University of Southampton and University Hospital Southampton NHS Foundation Trust, Southampton, UK.; Academic Unit of Human Development and Health, Faculty of Medicine, University of Southampton, Southampton, UK., Titcombe P; MRC Lifecourse Epidemiology Unit, University of Southampton, Southampton, UK., Melton PE; Centre for Genetics of Health and Disease, University of Western Australia, Perth, Australia.; Faculty of Health Science, Curtin University, Perth, WA, Australia., Murray RJS; Academic Unit of Human Development and Health, Faculty of Medicine, University of Southampton, Southampton, UK., Barton SJ; MRC Lifecourse Epidemiology Unit, University of Southampton, Southampton, UK., Clarke-Harris R; Academic Unit of Human Development and Health, Faculty of Medicine, University of Southampton, Southampton, UK., Costello PM; Academic Unit of Human Development and Health, Faculty of Medicine, University of Southampton, Southampton, UK., Holbrook JD; NIHR Southampton Biomedical Research Centre, University of Southampton and University Hospital Southampton NHS Foundation Trust, Southampton, UK.; Academic Unit of Human Development and Health, Faculty of Medicine, University of Southampton, Southampton, UK., Hopkins JC; Academic Unit of Human Development and Health, Faculty of Medicine, University of Southampton, Southampton, UK., Childs CE; Academic Unit of Human Development and Health, Faculty of Medicine, University of Southampton, Southampton, UK., Paras-Chavez C; Academic Unit of Human Development and Health, Faculty of Medicine, University of Southampton, Southampton, UK., Calder PC; NIHR Southampton Biomedical Research Centre, University of Southampton and University Hospital Southampton NHS Foundation Trust, Southampton, UK.; Academic Unit of Human Development and Health, Faculty of Medicine, University of Southampton, Southampton, UK., Mori TA; School of Medicine, University of Western Australia, Perth, WA, Australia., Beilin L; School of Medicine, University of Western Australia, Perth, WA, Australia., Burdge GC; Academic Unit of Human Development and Health, Faculty of Medicine, University of Southampton, Southampton, UK., Gluckman PD; Liggins Institute, University of Auckland, Auckland, New Zealand., Inskip HM; NIHR Southampton Biomedical Research Centre, University of Southampton and University Hospital Southampton NHS Foundation Trust, Southampton, UK.; MRC Lifecourse Epidemiology Unit, University of Southampton, Southampton, UK., Harvey NC; NIHR Southampton Biomedical Research Centre, University of Southampton and University Hospital Southampton NHS Foundation Trust, Southampton, UK.; MRC Lifecourse Epidemiology Unit, University of Southampton, Southampton, UK., Hanson MA; Academic Unit of Human Development and Health, Faculty of Medicine, University of Southampton, Southampton, UK., Huang RC; Telethon Kids Institute, University of Western Australia, Perth, WA, Australia., Cooper C; NIHR Southampton Biomedical Research Centre, University of Southampton and University Hospital Southampton NHS Foundation Trust, Southampton, UK.; MRC Lifecourse Epidemiology Unit, University of Southampton, Southampton, UK.; NIHR Biomedical Research Centre, University of Oxford, Oxford, UK., Godfrey KM; NIHR Southampton Biomedical Research Centre, University of Southampton and University Hospital Southampton NHS Foundation Trust, Southampton, UK.; MRC Lifecourse Epidemiology Unit, University of Southampton, Southampton, UK.
Jazyk: angličtina
Zdroj: International journal of obesity (2005) [Int J Obes (Lond)] 2019 May; Vol. 43 (5), pp. 974-988. Date of Electronic Publication: 2019 Jan 08.
DOI: 10.1038/s41366-018-0254-3
Abstrakt: 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.
Databáze: MEDLINE
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