Association analysis of positional obesity candidate genes based on integrated data from transcriptomics and linkage analysis

作者：Jiao H; Kaaman M; Dungner E; Kere J; Arner P^*; Dahlman I

来源：International Journal of Obesity, 2008, 32(5): 816-825.

DOI：10.1038/sj.ijo.0803789

• adipose tissue
• allelic association
• adiposity

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.

• 出版日期2008-5