Original Article
International Journal of Obesity (2008) 32, 816–825; doi:10.1038/sj.ijo.0803789; published online 8 January 2008
Association analysis of positional obesity candidate genes based on integrated data from transcriptomics and linkage analysis
H Jiao1, M Kaaman2, E Dungner2, J Kere1, P Arner2 and I Dahlman2
- 1Department of Biosciences and Nutrition, Clinical Research Center, Karolinska Institutet, Stockholm, Sweden
- 2Department of Medicine, Center for Metabolism and Endocrinology, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden
Correspondence: Professor P Arner, Department of Medicine, Center for Metabolism and Endocrinology MK-division, Karolinska Institutet, Karolinska University Hospital, Huddinge, M63, Stockholm SE-14186, Sweden. E-mail: peter.arner@ki.se
Received 2 April 2007; Revised 4 November 2007; Accepted 10 November 2007; Published online 8 January 2008.
Abstract
Context:
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.
Design:
Linkage and expression profile data from different cohorts were combined to select novel candidate genes that were analyzed for association with obesity.
Setting and participants:
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.
Main outcome measure:
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=<0.005).
Conclusion:
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.
Keywords:
adipose tissue, allelic association, adiposity
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