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Genetic Association and Gene Expression Analysis Identify FGFR1 as a New Susceptibility Gene for Human Obesity.

Artikel i vetenskaplig tidskrift
Författare Hong Jiao
Peter Arner
Suzanne L. Dickson
Hubert Vidal
Niklas Mejhert
Corneliu Henegar
Magdalena Taube
Caroline Hansson
Anke Hinney
Pilar Galan
Chantal Simon
Angela Silveira
Anna Benrick
John-Olov Jansson
Anne Bouloumié
Dominique Langin
Martine Laville
Cyrille Debard
Tomas Axelsson
Mikael Rydén
Juha Kere
Karin Dahlman-Wright
Anders Hamsten
Karine Clement
Ingrid Dahlman
Publicerad i The Journal of clinical endocrinology and metabolism
Volym 96
Nummer/häfte 6
Sidor E962-6
ISSN 1945-7197
Publiceringsår 2011
Publicerad vid Institutionen för neurovetenskap och fysiologi, sektionen för fysiologi
Sidor E962-6
Språk en
Länkar dx.doi.org/10.1210/jc.2010-2639
https://gup.ub.gu.se/file/95261
Ämneskategorier Medicinsk genetik

Sammanfattning

Context: Previous studies suggest a role for fibroblast growth factor receptor 1 (FGFR1) in the regulation of energy balance. Objective: Our objective was to investigate whether FGFR1 is an obesity gene by genetic association and functional studies. Design: The study was designed to genotype common FGFR1 single-nucleotide polymorphisms (SNP) in large cohorts, confirm significant results in additional cohorts, and measure FGFR1 expression in human adipose tissue and in rodent hypothalamus. Setting: General community and referral centers for specialized care was the setting for the study. Participants: We genotyped FGFR1 SNP in 2438 obese and 2115 lean adults and 985 obese and 532 population-based children. Results were confirmed in 928 obese and 2738 population-based adults and 487 obese and 441 lean children. Abdominal sc adipose tissue was investigated in 202 subjects. We also investigated diet-induced, obese fasting, and fed rats. Main Outcome Measures: We analyzed the association between FGFR1 SNP and obesity. In secondary analyses, we related adipose FGFR1 expression to genotype, obesity, and degree of fat cell differentiation and related hypothalamic FGFR1 to energy balance. Results: FGFR1 rs7012413*T was nominally associated with obesity in all four cohorts; metaanalysis odds ratio = 1.17 (95 % confidence interval = 1.10-1.25), and P = 1.8 × 10(-6), which was P = 7.0 × 10(-8) in the recessive model. rs7012413*T was associated with FGFR1 expression in adipose tissue (P < 0.0001). In this organ, but not in skeletal muscle, FGFR1 mRNA (P < 0.0001) and protein (P < 0.05) were increased in obesity. In rats, hypothalamic expression of FGFR1 declined after fasting (P < ]0.001) and increased after diet-induced obesity (P < 0.05). Conclusions: FGFR1 is a novel obesity gene that may promote obesity by influencing adipose tissue and the hypothalamic control of appetite.

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