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=or<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.
