Please use this identifier to cite or link to this item: https://doi.org/10.1038/s41366-018-0254-3
Title: Differential SLC6A4 methylation: a predictive epigenetic marker of adiposity from birth to adulthood
Authors: Lillycrop, Karen A
Garratt, Emma S
Titcombe, Philip
Melton, Phillip E
Murray, Robert JS
Barton, Sheila J
Clarke-Harris, Rebecca
Costello, Paula M
Holbrook, Joanna D 
Hopkins, James C
Childs, Caroline E
Paras-Chavez, Carolina
Calder, Philip C
Mori, Trevor A
Beilin, Lawrie
Burdge, Graham C
Gluckman, Peter D 
Inskip, Hazel M
Harvey, Nicholas C
Hanson, Mark A
Huang, Rae-Chi
Cooper, Cyrus
Godfrey, Keith M
Burdge, Graham
Seng, Chong Yap 
Cutfield, Wayne
Godfrey, Keith
Harvey, Nicholas
Foong-Fong, Mary Chong 
Karnani, Neerja 
Seng, Lee Yung 
Stunkel, Walter
Shepherd, Allan
Keywords: Science & Technology
Life Sciences & Biomedicine
Endocrinology & Metabolism
Nutrition & Dietetics
SEROTONIN TRANSPORTER GENE
PROTEIN-RESTRICTED DIET
GENOME-WIDE ASSOCIATION
PROMOTER METHYLATION
NEONATAL ADIPOSITY
DNA METHYLATION
OBESITY
RISK
CHILDHOOD
WEIGHT
Issue Date: 1-May-2019
Publisher: SPRINGERNATURE
Citation: Lillycrop, Karen A, Garratt, Emma S, Titcombe, Philip, Melton, Phillip E, Murray, Robert JS, Barton, Sheila J, Clarke-Harris, Rebecca, Costello, Paula M, Holbrook, Joanna D, Hopkins, James C, Childs, Caroline E, Paras-Chavez, Carolina, Calder, Philip C, Mori, Trevor A, Beilin, Lawrie, Burdge, Graham C, Gluckman, Peter D, Inskip, Hazel M, Harvey, Nicholas C, Hanson, Mark A, Huang, Rae-Chi, Cooper, Cyrus, Godfrey, Keith M, Burdge, Graham, Seng, Chong Yap, Cutfield, Wayne, Godfrey, Keith, Harvey, Nicholas, Foong-Fong, Mary Chong, Karnani, Neerja, Seng, Lee Yung, Stunkel, Walter, Shepherd, Allan (2019-05-01). Differential SLC6A4 methylation: a predictive epigenetic marker of adiposity from birth to adulthood. INTERNATIONAL JOURNAL OF OBESITY 43 (5) : 974-988. ScholarBank@NUS Repository. https://doi.org/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.
Source Title: INTERNATIONAL JOURNAL OF OBESITY
URI: https://scholarbank.nus.edu.sg/handle/10635/216137
ISSN: 03070565
14765497
DOI: 10.1038/s41366-018-0254-3
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