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Major gender difference in association of FTO gene variant among severely obese children with obesity and obesity related phenotypes.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience.
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2008 (English)In: Biochemical and Biophysical Research Communications - BBRC, ISSN 0006-291X, E-ISSN 1090-2104, Vol. 368, no 3, 476-482 p.Article in journal (Refereed) Published
Abstract [en]

Recent studies have shown that SNPs in the FTO gene predispose to childhood and adult obesity. In this study, we examined the association between variants in FTO and KIAA1005, a gene that maps closely to FTO, and obesity, as well as obesity related traits among 450 well characterised severely obese children and 512 normal weight controls. FTO showed significant association with several obesity related traits while SNPs in KIAA1005 did not. When stratified by gender, the FTO variant rs9939609 showed association with obesity and BMI among girls (P=0.006 and 0.004, respectively) but not among boys. Gender differences were also found in the associations of the FTO rs9939609 with obesity related traits such as insulin sensitivity and plasma glucose. This study suggests that FTO may have an important role for gender specific development of severe obesity and insulin resistance in children.

Place, publisher, year, edition, pages
2008. Vol. 368, no 3, 476-482 p.
Keyword [en]
FTO, obesity, SNP, diabetes, children, body mass index, insulin, glucose
National Category
Medical and Health Sciences
URN: urn:nbn:se:uu:diva-99137DOI: 10.1016/j.bbrc.2008.01.087ISI: 000253925900005PubMedID: 18249188OAI: oai:DiVA.org:uu-99137DiVA: diva2:202263
Available from: 2009-03-09 Created: 2009-03-09 Last updated: 2011-05-05Bibliographically approved
In thesis
1. Obesity and Increased Susceptibility : Role of FTO and MGAT1 Genetic Variants
Open this publication in new window or tab >>Obesity and Increased Susceptibility : Role of FTO and MGAT1 Genetic Variants
2011 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Obesity is a complex and a highly individualized disease and the molecular mechanisms behind this disorder need to be better elucidated. Identification of genes and genetic variants that are involved provide opportunities to establish a genetic understanding of the disease. These findings may also provide more rational approaches to therapy, either by identifying underlying causes or point out the need for different treatments. In addition, the timing and severity of obesity may provide insights into the aetiology of obesity and also identify age-specific determinants of weight gain. Recently, genome-wide association studies have led to a rapid progress in our understanding of the genetic basis of various diseases and candidate genes for obesity have been identified. The overall aim of this thesis was to investigate the genetic impact on severity of childhood obesity and the associations between obesity and genetic variants in the fat mass and obesity associated gene, FTO, and MGAT1, the gene encoding mannosyl (α-1,3-)-glycoprotein β-1,2-N-acetyl-glucosaminyltransferase.

We show that the impact of parental body mass index (BMI) on the severity of obesity in children is strengthened as the child grows older, whereas the age at obesity onset is of limited importance.

By association studies, we show that single nucleotide polymorphisms downstream MGAT1 influence susceptibility to obesity. Moreover, these variants affect the levels of unsaturated fatty acids and desaturase indices, variables previously shown to correlate with obesity. Furthermore, one variant in the first intronic region of FTO is associated with obesity among children but not with BMI or other measures of adiposity at older ages. However, this variant shows a weight-dependent association with cognitive function among elderly men. By direct sequencing, we identified novel variants in FTO, affecting glucose homeostasis in a BMI-independent manner. Furthermore, we found gender specific effects for FTO, both regarding obesity susceptibility and related phenotypes.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2011. 68 p.
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 658
Obesity, BMI, SNP, haplotype, association study, FTO, MGAT1
National Category
Pharmacology and Toxicology
Research subject
urn:nbn:se:uu:diva-149332 (URN)978-91-554-8039-4 (ISBN)
Public defence
2011-05-07, B22, BMC, Husargatan 3, Uppsala, 09:00 (English)
Available from: 2011-04-14 Created: 2011-03-17 Last updated: 2011-06-13Bibliographically approved

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Jacobsson, Josefin A.
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Functional PharmacologyDepartment of NeuroscienceDepartment of Genetics and Pathology
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