Differential SLC6A4 methylation: a predictive epigenetic marker of adiposity from birth to adulthood
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...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , |
|---|---|
| Format: | Journal Article |
| Published: |
Nature Publishing Group
2019
|
| Online Access: | http://hdl.handle.net/20.500.11937/74636 |
| _version_ | 1848763330539290624 |
|---|---|
| author | Lillycrop, K. Garratt, E. Titcombe, P. Melton, Phillip Murray, R. Barton, S. Clarke-Harris, R. Costello, P. Holbrook, J. Hopkins, J. Childs, C. Paras-Chavez, C. Calder, P. Mori, T. Beilin, L. Burdge, G. Gluckman, P. Inskip, H. Harvey, N. Hanson, M. Huang, R. Cooper, C. Godfrey, K. |
| author_facet | Lillycrop, K. Garratt, E. Titcombe, P. Melton, Phillip Murray, R. Barton, S. Clarke-Harris, R. Costello, P. Holbrook, J. Hopkins, J. Childs, C. Paras-Chavez, C. Calder, P. Mori, T. Beilin, L. Burdge, G. Gluckman, P. Inskip, H. Harvey, N. Hanson, M. Huang, R. Cooper, C. Godfrey, K. |
| author_sort | Lillycrop, K. |
| building | Curtin Institutional Repository |
| collection | Online Access |
| description | 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. |
| first_indexed | 2025-11-14T11:01:45Z |
| format | Journal Article |
| id | curtin-20.500.11937-74636 |
| institution | Curtin University Malaysia |
| institution_category | Local University |
| last_indexed | 2025-11-14T11:01:45Z |
| publishDate | 2019 |
| publisher | Nature Publishing Group |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | curtin-20.500.11937-746362019-06-24T08:15:41Z Differential SLC6A4 methylation: a predictive epigenetic marker of adiposity from birth to adulthood Lillycrop, K. Garratt, E. Titcombe, P. Melton, Phillip Murray, R. Barton, S. Clarke-Harris, R. Costello, P. Holbrook, J. Hopkins, J. Childs, C. Paras-Chavez, C. Calder, P. Mori, T. Beilin, L. Burdge, G. Gluckman, P. Inskip, H. Harvey, N. Hanson, M. Huang, R. Cooper, C. Godfrey, K. 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. 2019 Journal Article http://hdl.handle.net/20.500.11937/74636 10.1038/s41366-018-0254-3 http://creativecommons.org/licenses/by/4.0/ Nature Publishing Group fulltext |
| spellingShingle | Lillycrop, K. Garratt, E. Titcombe, P. Melton, Phillip Murray, R. Barton, S. Clarke-Harris, R. Costello, P. Holbrook, J. Hopkins, J. Childs, C. Paras-Chavez, C. Calder, P. Mori, T. Beilin, L. Burdge, G. Gluckman, P. Inskip, H. Harvey, N. Hanson, M. Huang, R. Cooper, C. Godfrey, K. Differential SLC6A4 methylation: a predictive epigenetic marker of adiposity from birth to adulthood |
| title | Differential SLC6A4 methylation: a predictive epigenetic marker of adiposity from birth to adulthood |
| title_full | Differential SLC6A4 methylation: a predictive epigenetic marker of adiposity from birth to adulthood |
| title_fullStr | Differential SLC6A4 methylation: a predictive epigenetic marker of adiposity from birth to adulthood |
| title_full_unstemmed | Differential SLC6A4 methylation: a predictive epigenetic marker of adiposity from birth to adulthood |
| title_short | Differential SLC6A4 methylation: a predictive epigenetic marker of adiposity from birth to adulthood |
| title_sort | differential slc6a4 methylation: a predictive epigenetic marker of adiposity from birth to adulthood |
| url | http://hdl.handle.net/20.500.11937/74636 |