PMID- 25866590
OWN - NLM
STAT- PubMed-not-MEDLINE
DCOM- 20150413
LR  - 20181113
IS  - 1868-7075 (Print)
IS  - 1868-7083 (Electronic)
IS  - 1868-7075 (Linking)
VI  - 7
IP  - 1
DP  - 2015
TI  - Genome-wide blood DNA methylation alterations at regulatory elements and 
      heterochromatic regions in monozygotic twins discordant for obesity and liver 
      fat.
PG  - 39
LID - 10.1186/s13148-015-0073-5 [doi]
LID - 39
AB  - BACKGROUND: The current epidemic of obesity and associated diseases calls for 
      swift actions to better understand the mechanisms by which genetics and 
      environmental factors affect metabolic health in humans. Monozygotic (MZ) twin 
      pairs showing discordance for obesity suggest that epigenetic influences 
      represent one such mechanism. We studied genome-wide leukocyte DNA methylation 
      variation in 30 clinically healthy young adult MZ twin pairs discordant for body 
      mass index (BMI; average within-pair BMI difference: 5.4 +/- 2.0 kg/m(2)). RESULTS: 
      There were no differentially methylated cytosine-guanine (CpG) sites between the 
      co-twins discordant for BMI. However, stratification of the twin pairs based on 
      the level of liver fat accumulation revealed two epigenetically highly different 
      groups. Significant DNA methylation differences (n = 1,236 CpG sites (CpGs)) 
      between the co-twins were only observed if the heavier co-twins had excessive 
      liver fat (n = 13 twin pairs). This unhealthy pattern of obesity was coupled with 
      insulin resistance and low-grade inflammation. The differentially methylated CpGs 
      included 23 genes known to be associated with obesity, liver fat, type 2 diabetes 
      mellitus (T2DM) and metabolic syndrome, and potential novel metabolic genes. 
      Differentially methylated CpG sites were overrepresented at promoters, 
      insulators, and heterochromatic and repressed regions. Based on predictions by 
      overlapping histone marks, repressed and weakly transcribed sites were 
      significantly more often hypomethylated, whereas sites with strong enhancers and 
      active promoters were hypermethylated. Further, significant clustering of 
      differentially methylated genes in vitamin, amino acid, fatty acid, sulfur, and 
      renin-angiotensin metabolism pathways was observed. CONCLUSIONS: The methylome in 
      leukocytes is altered in obesity associated with metabolic disturbances, and our 
      findings indicate several novel candidate genes and pathways in obesity and 
      obesity-related complications.
FAU - Ollikainen, Miina
AU  - Ollikainen M
AD  - Department of Public Health, University of Helsinki, Helsinki, Finland.
FAU - Ismail, Khadeeja
AU  - Ismail K
AD  - Department of Public Health, University of Helsinki, Helsinki, Finland.
FAU - Gervin, Kristina
AU  - Gervin K
AD  - Department of Medical Genetics, Oslo University Hospital and University of Oslo, 
      Oslo, Norway.
FAU - Kyllonen, Anjuska
AU  - Kyllonen A
AD  - Obesity Research Unit, Research Programs Unit, Diabetes and Obesity, University 
      of Helsinki, Helsinki, Finland.
FAU - Hakkarainen, Antti
AU  - Hakkarainen A
AD  - Department of Radiology, HUS Medical Imaging Center, Helsinki University Central 
      Hospital, University of Helsinki, Helsinki, Finland.
FAU - Lundbom, Jesper
AU  - Lundbom J
AD  - Department of Radiology, HUS Medical Imaging Center, Helsinki University Central 
      Hospital, University of Helsinki, Helsinki, Finland.
FAU - Jarvinen, Elina A
AU  - Jarvinen EA
AD  - Obesity Research Unit, Research Programs Unit, Diabetes and Obesity, University 
      of Helsinki, Helsinki, Finland.
FAU - Harris, Jennifer R
AU  - Harris JR
AD  - Division of Epidemiology, The Norwegian Institute of Public Health, Oslo, Norway.
FAU - Lundbom, Nina
AU  - Lundbom N
AD  - Department of Radiology, HUS Medical Imaging Center, Helsinki University Central 
      Hospital, University of Helsinki, Helsinki, Finland.
FAU - Rissanen, Aila
AU  - Rissanen A
AD  - Department of Psychiatry, Helsinki University Central Hospital, Helsinki, 
      Finland.
AD  - Endocrinology, Abdominal Center, Helsinki University Central Hospital, Helsinki, 
      Finland.
FAU - Lyle, Robert
AU  - Lyle R
AD  - Department of Medical Genetics, Oslo University Hospital and University of Oslo, 
      Oslo, Norway.
FAU - Pietilainen, Kirsi H
AU  - Pietilainen KH
AD  - Obesity Research Unit, Research Programs Unit, Diabetes and Obesity, University 
      of Helsinki, Helsinki, Finland.
AD  - Endocrinology, Abdominal Center, Helsinki University Central Hospital, Helsinki, 
      Finland.
AD  - Institute for Molecular Medicine FIMM, University of Helsinki, Helsinki, Finland.
FAU - Kaprio, Jaakko
AU  - Kaprio J
AD  - Department of Public Health, University of Helsinki, Helsinki, Finland.
AD  - Institute for Molecular Medicine FIMM, University of Helsinki, Helsinki, Finland.
AD  - Department of Mental Health and Substance Abuse Services, National Institute for 
      Health and Welfare, Helsinki, Finland.
LA  - eng
PT  - Journal Article
DEP - 20150402
PL  - Germany
TA  - Clin Epigenetics
JT  - Clinical epigenetics
JID - 101516977
PMC - PMC4393626
OTO - NOTNLM
OT  - DNA methylation
OT  - Epigenetics
OT  - Liver fat
OT  - Monozygotic twins
OT  - Obesity
EDAT- 2015/04/14 06:00
MHDA- 2015/04/14 06:01
PMCR- 2015/04/02
CRDT- 2015/04/14 06:00
PHST- 2014/10/17 00:00 [received]
PHST- 2015/03/11 00:00 [accepted]
PHST- 2015/04/14 06:00 [entrez]
PHST- 2015/04/14 06:00 [pubmed]
PHST- 2015/04/14 06:01 [medline]
PHST- 2015/04/02 00:00 [pmc-release]
AID - 73 [pii]
AID - 10.1186/s13148-015-0073-5 [doi]
PST - epublish
SO  - Clin Epigenetics. 2015 Apr 2;7(1):39. doi: 10.1186/s13148-015-0073-5. eCollection 
      2015.