Novel genetic variant in FTO influences insulin levels and insulin resistance in severely obese children and adolescents
(2008) In International Journal of Obesity 32(11). p.1730-1735- Abstract
- 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... (More)
- 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 andadolescents 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. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/1308670
- author
- Jacobsson, J. A. ; Klovins, J. ; Kapa, I. ; Danielsson, P. ; Svensson, V. ; Ridderstråle, Martin LU ; Gyllensten, U. ; Marcus, C. ; Fredriksson, R. and Schioth, H. B.
- organization
- publishing date
- 2008
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- adolescents, children, metabolic phenotypes, FTO, polymorphism
- in
- International Journal of Obesity
- volume
- 32
- issue
- 11
- pages
- 1730 - 1735
- publisher
- Nature Publishing Group
- external identifiers
-
- wos:000260925300019
- scopus:56549107150
- pmid:18794893
- ISSN
- 1476-5497
- DOI
- 10.1038/ijo.2008.168
- language
- English
- LU publication?
- yes
- id
- 4453002d-9175-4585-8998-7149cd07d6d6 (old id 1308670)
- date added to LUP
- 2016-04-01 11:57:20
- date last changed
- 2022-01-26 20:43:53
@article{4453002d-9175-4585-8998-7149cd07d6d6,
abstract = {{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 andadolescents 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.}},
author = {{Jacobsson, J. A. and Klovins, J. and Kapa, I. and Danielsson, P. and Svensson, V. and Ridderstråle, Martin and Gyllensten, U. and Marcus, C. and Fredriksson, R. and Schioth, H. B.}},
issn = {{1476-5497}},
keywords = {{adolescents; children; metabolic phenotypes; FTO; polymorphism}},
language = {{eng}},
number = {{11}},
pages = {{1730--1735}},
publisher = {{Nature Publishing Group}},
series = {{International Journal of Obesity}},
title = {{Novel genetic variant in FTO influences insulin levels and insulin resistance in severely obese children and adolescents}},
url = {{http://dx.doi.org/10.1038/ijo.2008.168}},
doi = {{10.1038/ijo.2008.168}},
volume = {{32}},
year = {{2008}},
}