Novel genetic variant in FTO influences insulin levels and insulin resistance in severely obese children and adolescents

• Published in: INTERNATIONAL JOURNAL OF OBESITY Vol. 32; no. 11; pp. 1730 - 1735
• Main Authors: Jacobsson, J.A, Klovins, J, Kapa, I, Danielsson, P, Svensson, V, Ridderstrale, M, Gyllensten, U, Marcus, C, Fredriksson, R, Schioth, H.B
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.11.2008; Nature Publishing Group
• Subjects: Adolescent; adolescent nutrition; Adolescents; Biological and medical sciences; Blood Glucose - genetics; Body Mass Index; Boundaries; Child; child nutrition; Children; Cholesterol; Diabetes; diet-related diseases; Epidemiology; exons; Female; FTO; FTO gene; General aspects; genes; Genetic aspects; genetic polymorphism; Genetic polymorphisms; Genetic Predisposition to Disease; Genetic variance; Genetic Variation; Genome-Wide Association Study; Genomes; Genotype & phenotype; Glucose; Health Promotion and Disease Prevention; Health Sciences; human diseases; Humans; Hälsovetenskap; insulin; Insulin resistance; Insulin Resistance - genetics; Internal Medicine; Lipoproteins; Male; Medical and Health Sciences; Medical sciences; MEDICIN; Medicin och hälsovetenskap; MEDICINE; Medicine & Public Health; Metabolic Diseases; metabolic phenotypes; Metabolism; molecular sequence data; Neurosciences; Nutrition and Dietetics; nutrition-genotype interaction; Näringslära; Obesity; Obesity - genetics; Overweight; Phenotype; Polymorphism; Polymorphism, Single Nucleotide - genetics; Public Health; Risk factors; short-communication; Standard deviation; Teenagers; Triglycerides; Young Adult; Sweden; Latvia; polymorphism; metabolic phenotypes; children; adolescents; Endocrinopathy; Human; FTO; Obesity; Pancreatic hormone; Genetic variability; Nutrition; Genetic variant; Nutrition disorder; Genotype; Metabolic diseases; Metabolism; Insulin; Target tissue resistance; Phenotype; Adolescent; Insulin resistance; Child; Nutritional status; Polymorphism
• ISSN: 0307-0565; 1476-5497; 1476-5497
• DOI: 10.1038/ijo.2008.168

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.