BACKGROUND: The global prevalence of obesity and overweight is increasing rapidly among adults as well as among children and adolescents. Recent genome-wide association studies have provided strong support for association between variants in the FTO gene and obesity. We sequenced regions of the FTO gene to identify novel variants that are associated with obesity and related metabolic traits. RESULTS: We screened exons 3 and 4 including exon-intron boundaries in FTO in 48 obese children and adolescents and identified three novel single nucleotide polymorphism in the fourth intronic region, (c.896+37A>G, c.896+117C>G and c.896+223A>G). We further genotyped c.896+223A>G in 962 subjects, 450 well-characterized obese children and adolescents and 512 adolescents with normal weight. Evidence for differences in genotype frequencies were not detected for the c.896+223A>G variant between extremely obese children and adolescents and normal weight adolescents (P=0.406, OR=1.154 (0.768-1.736)). Obese subjects with the GG genotype, however, had 30% increased fasting serum insulin levels (P=0.017) and increased degree of insulin resistance (P=0.025). There were in addition no differences in body mass index (BMI) or BMI standard deviation score (SDS) levels among the obese subjects according to genotype and the associations with insulin levels and insulin resistance remained significant when adjusting for BMI SDS. CONCLUSION: These findings suggest that this novel variant in FTO is affecting metabolic phenotypes such as insulin resistance, which are not mediated through differences in BMI levels.
BACKGROUND: The global prevalence of obesity and overweight is increasing rapidly among adults as well as among children and adolescents. Recent genome-wide association studies have provided strong support for association between variants in the FTO gene and obesity. We sequenced regions of the FTO gene to identify novel variants that are associated with obesity and related metabolic traits. RESULTS: We screened exons 3 and 4 including exon-intron boundaries in FTO in 48 obesechildren and adolescents and identified three novel single nucleotide polymorphism in the fourth intronic region, (c.896+37A>G, c.896+117C>G and c.896+223A>G). We further genotyped c.896+223A>G in 962 subjects, 450 well-characterized obesechildren and adolescents and 512 adolescents with normal weight. Evidence for differences in genotype frequencies were not detected for the c.896+223A>G variant between extremely obesechildren and adolescents and normal weight adolescents (P=0.406, OR=1.154 (0.768-1.736)). Obese subjects with the GG genotype, however, had 30% increased fasting serum insulin levels (P=0.017) and increased degree of insulin resistance (P=0.025). There were in addition no differences in body mass index (BMI) or BMI standard deviation score (SDS) levels among the obese subjects according to genotype and the associations with insulin levels and insulin resistance remained significant when adjusting for BMI SDS. CONCLUSION: These findings suggest that this novel variant in FTO is affecting metabolic phenotypes such as insulin resistance, which are not mediated through differences in BMI levels.
Authors: Anke Tönjes; Eleftheria Zeggini; Peter Kovacs; Yvonne Böttcher; Dorit Schleinitz; Kerstin Dietrich; Andrew P Morris; Beate Enigk; Nigel W Rayner; Moritz Koriath; Markus Eszlinger; Anu Kemppinen; Inga Prokopenko; Katrin Hoffmann; Daniel Teupser; Joachim Thiery; Knut Krohn; Mark I McCarthy; Michael Stumvoll Journal: Eur J Hum Genet Date: 2010-01 Impact factor: 4.246
Authors: Gaifen Liu; Haidong Zhu; Vasiliki Lagou; Bernard Gutin; Inger S Stallmann-Jorgensen; Frank A Treiber; Yanbin Dong; Harold Snieder Journal: BMC Med Genet Date: 2010-04-09 Impact factor: 2.103
Authors: Mathias Rask-Andersen; Josefin A Jacobsson; George Moschonis; Anna E Ek; George P Chrousos; Claude Marcus; Yannis Manios; Robert Fredriksson; Helgi B Schiöth Journal: BMC Med Genet Date: 2012-05-17 Impact factor: 2.103
Authors: Pawel K Olszewski; Robert Fredriksson; Agnieszka M Olszewska; Olga Stephansson; Johan Alsiö; Katarzyna J Radomska; Allen S Levine; Helgi B Schiöth Journal: BMC Neurosci Date: 2009-10-27 Impact factor: 3.288