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

• Published in: International Journal of Obesity Vol. 32; no. 5; pp. 816 - 825
• Main Authors: Jiao, H, Kaaman, M, Dungner, E, Kere, J, Arner, P, Dahlman, I
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.05.2008; Nature Publishing; Nature Publishing Group
• Subjects: Adipose tissue; Adipose tissues; Adult; alleles; Biological and medical sciences; biological resistance; Body fat; Body mass index; cohort studies; Diagnosis; disease resistance; Endocrinology; Epidemiologic Methods; epidemiological studies; Epidemiology; Female; Gene expression; Gene Expression Profiling - methods; gene frequency; Gene loci; Genetic aspects; genetic correlation; Genetic Linkage - genetics; Genetic Predisposition to Disease - genetics; Genotype; glycolysis; Health Promotion and Disease Prevention; Humans; Internal Medicine; Kinases; linkage (genetics); Male; Medical sciences; Medicin och hälsovetenskap; Medicine; Medicine & Public Health; messenger RNA; Metabolic Diseases; Metabolism; Obesity; Obesity - genetics; Obesity - metabolism; obesity genes; obesity-related diseases; original-article; pathogenesis; Phosphofructokinase-2 - genetics; Phosphofructokinase-2 - metabolism; Physiological aspects; Public Health; quantitative trait loci; quantitative traits; Risk factors; RNA, Messenger - genetics; single nucleotide polymorphism; transcriptomics; Westernization; women; Sweden; adipose tissue; allelic association; adiposity; Medical data; Human; Obesity; Data analysis; Adipose tissue; Nutrition; Nutrition disorder; Metabolic diseases; Linkage equilibrium; Association; Adiposity; Genetic linkage; Genetics; Candidate gene; Nutritional status
• ISSN: 0307-0565; 1476-5497; 1476-5497
• DOI: 10.1038/sj.ijo.0803789

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 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.