CCAAT/enhancer binding protein alpha, beta and delta gene variants: associations with obesity related phenotypes in the Leeds Family Study.
OBJECTIVE
To identify novel polymorphisms in the genes encoding the transcription factors CCAAT/enhancer binding protein alpha, beta and delta ( CEBPA, CEBPB, CEBPD) and investigate associations between polymorphisms and obesity-related phenotypes.


METHODS
Denaturing high-performance liquid chromatography (HPLC) was used to screen for novel gene variants and polymorphisms were genotyped in stored DNA from participants of the Leeds Family Study (537 subjects from 89 families). Genotype and haplotype analyses were carried out in STATA and PBAT, respectively.


RESULTS
Twenty-five polymorphisms were identified; 11 in CEBPA, 12 in CEBPB and 2 in CEBPD. Several allelic variants were associated at a nominal 5% level with waist-to-hip ratio (-919G>A in CEBPA, -412G>T and 646C>T in CEBPB), leptin (1558G>A in CEBPA, -1051A>G and 1383T>- in CEBPB) and adiponectin (1382G>T and 1903G>T in CEBPB). Effects of CEBPA and CEBPB allelic variants were independent, but variants within each gene were in linkage disequilibrium. Several associations were observed between other obesity-related traits and allelic variants in CEBPA and CEBPB, but not CEBPD.


CONCLUSIONS
These findings suggest that common allelic variants in CEBPA and CEBPB could influence abdominal obesity and related metabolic abnormalities associated with type 2 diabetes and cardiovascular disease in healthy White Northern European families, although results require independent confirmation.
Bennett
Claire E
CE
Division of Cardiovascular and Diabetes Research, Leeds Institute of Genetics, Health and Therapeutics, University of Leeds, UK.
Nsengimana
Jérémie
J
Bostock
Jacqueline A
JA
Cymbalista
Charlotte
C
Futers
T Simon
TS
Knight
Bernice L
BL
McCormack
Lynn J
LJ
Prasad
Usha K
UK
Riches
Kirsten
K
Rolton
Daniel
D
Scarrott
Thomas
T
Barrett
Jennifer H
JH
Carter
Angela M
AM
D052242:Adiponectin / Q000097:blood; D022782:CCAAT-Enhancer-Binding Protein-beta / Q000235:genetics*; D051743:CCAAT-Enhancer-Binding Protein-delta / Q000235:genetics*; D022762:CCAAT-Enhancer-Binding Proteins / Q000235:genetics*; D002851:Chromatography, High Pressure Liquid; D004739:England / Q000453:epidemiology; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006801:Humans; D020738:Leptin / Q000097:blood; D016014:Linear Models; D015810:Linkage Disequilibrium; D009765:Obesity / Q000097:blood / Q000208:ethnology / Q000235:genetics* / Q000503:physiopathology; D010375:Pedigree; D010641:Phenotype; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D018570:Risk Assessment; D012307:Risk Factors; D049629:Waist-Hip Ratio; D044465:White People / Q000235:genetics
C499918:ADIPOQ protein, human; D052242:Adiponectin; D022782:CCAAT-Enhancer-Binding Protein-beta; D022762:CCAAT-Enhancer-Binding Proteins; C515848:CEBPA protein, human; C545012:CEBPB protein, human; C497252:CEBPD protein, human; D020738:Leptin; D051743:CCAAT-Enhancer-Binding Protein-delta