Association analysis of positional obesity candidate genes based on integrated data from transcriptomics and linkage analysis.
BACKGROUND
Obesity is a typical complex disorder resulting from behaviors promoted in westernized societies in the presence of a genetic predisposition. We hypothesized that new genes predisposing to obesity can be detected at the mRNA level.


OBJECTIVE
To identify susceptibility genes for obesity.


METHODS
Linkage and expression profile data from different cohorts were combined to select novel candidate genes that were analyzed for association with obesity.


METHODS
University Hospital in Stockholm. Adipose tissue mRNA levels were quantified in 96 women. Two large cohorts with a wide distribution in body mass index (BMI, n=1013 and 1423) were genotyped.


METHODS
mRNA levels and allelic association with obesity.


RESULTS
We confirmed association between candidate gene mRNA levels in adipose tissue and obesity. A total of 118 polymorphisms in 16 genes were analyzed for association with obesity. Single nucleotide polymorphism rs1064891, located in the 3' UTR of the 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 (PFKFB3) gene, was nominally associated with obesity in combined analysis of cohorts 1 and 2 (P=0.007) and, in men that were lean or had severe obesity, with BMI (P=or<0.005).


CONCLUSIONS
To combine linkage and expression profile data is valuable in finding new obesity genes. PFKFB3, a potential regulator of glycolysis, displays decreased mRNA levels in adipose tissue of obese women, is associated with obesity and is a new promising candidate gene for obesity warranting further studies.
Jiao
H
H
Department of Biosciences and Nutrition, Clinical Research Center, Karolinska Institutet, Stockholm, Sweden.
Kaaman
M
M
Dungner
E
E
Kere
J
J
Arner
P
P
Dahlman
I
I
D000328:Adult; D004812:Epidemiologic Methods; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods*; D008040:Genetic Linkage / Q000235:genetics*; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D006801:Humans; D008297:Male; D009765:Obesity / Q000235:genetics* / Q000378:metabolism; D025481:Phosphofructokinase-2 / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics
D012333:RNA, Messenger; C107345:PFKFB3 protein, human; D025481:Phosphofructokinase-2