Differential SLC6A4 methylation: a predictive epigenetic marker of adiposity from birth to adulthood.
Absorptiometry, Photon
Adiposity
/ genetics
Adolescent
Adult
Australia
/ epidemiology
Biomarkers
/ metabolism
Child
Child, Preschool
Cohort Studies
DNA Methylation
/ genetics
Epigenesis, Genetic
/ physiology
Female
Gene-Environment Interaction
Genetic Predisposition to Disease
Humans
Infant, Newborn
Male
Metabolic Diseases
/ epidemiology
Obesity
/ epidemiology
Promoter Regions, Genetic
/ genetics
Serotonin Plasma Membrane Transport Proteins
/ metabolism
Journal
International journal of obesity (2005)
ISSN: 1476-5497
Titre abrégé: Int J Obes (Lond)
Pays: England
ID NLM: 101256108
Informations de publication
Date de publication:
05 2019
05 2019
Historique:
received:
13
02
2018
accepted:
26
08
2018
revised:
21
08
2018
pubmed:
10
1
2019
medline:
28
3
2020
entrez:
10
1
2019
Statut:
ppublish
Résumé
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. 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. 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. These data suggest that altered methylation of CpG loci within SLC6A4 may provide a robust marker of adiposity across the life course.
Sections du résumé
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.
Identifiants
pubmed: 30622309
doi: 10.1038/s41366-018-0254-3
pii: 10.1038/s41366-018-0254-3
pmc: PMC6522375
mid: EMS79322
doi:
Substances chimiques
Biomarkers
0
SLC6A4 protein, human
0
Serotonin Plasma Membrane Transport Proteins
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
974-988Subventions
Organisme : Versus Arthritis
ID : 17702
Pays : United Kingdom
Organisme : British Heart Foundation
ID : PG/14/33/30827
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_U147585827
Pays : United Kingdom
Organisme : NIA NIH HHS
ID : U24 AG047867
Pays : United States
Organisme : Medical Research Council
ID : MC_UU_12011/2
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_ST_U12055
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_UP_A620_1014
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_UP_A620_1017
Pays : United Kingdom
Organisme : Department of Health
ID : NF-SI-0515-10042
Pays : United Kingdom
Organisme : British Heart Foundation
ID : RG/07/009
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_UU_12011/4
Pays : United Kingdom
Organisme : British Heart Foundation
ID : RG/15/17/31749
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_UP_A620_1015
Pays : United Kingdom
Organisme : Biotechnology and Biological Sciences Research Council
ID : ES/M00919X/1
Pays : United Kingdom
Organisme : Versus Arthritis
ID : 21231
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_U147585819
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_U147574226
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_U147574222
Pays : United Kingdom
Organisme : British Heart Foundation
ID : RG/07/009/23120
Pays : United Kingdom
Organisme : Department of Health
ID : 10/33/04
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_UU_12011/1
Pays : United Kingdom
Organisme : Medical Research Council
ID : G0400491
Pays : United Kingdom
Organisme : British Heart Foundation
ID : RG/15/17/3174
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_U147585824
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/J000094/1
Pays : United Kingdom
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