Influence of FTO variants on obesity, inflammation and cardiovascular disease risk biomarkers in Spanish children: a case–control multicentre study

BMC Medical Genetics

Concepcion M Aguilera³  Angel Gil³  Ramon Cañete²  Rafael Tojo¹  Dietmar Fernandez-Orth⁴  Rosaura Leis¹  Mercedes Gil-Campos²  Azahara I Ruperez³  Josune Olza³ 

[1] Unit of Investigation in Nutrition, Growth and Human Development of Galicia, Paediatric Department, Clinic University Hospital of Santiago, University of Santiago de Compostela, Galicia, Spain;Paediatric Research and Metabolism Unit, Reina Sofía University Hospital, Maimonides Institute for Biomedical Research (IMIBIC), Córdoba, Spain;Department of Biochemistry and Molecular Biology II, Faculty of Pharmacy Institute of Nutrition and Food Technology, University of Granada, Granada, Spain;Progenika Biopharma S.A, Building 504, Zamudio Technologic Park. Derio, Bizkaia, Spain

关键词: CVD;    Inflammation;    Child;    Obesity;    Genetic polymorphism;    FTO;   

Others  :  1122568
DOI  :  10.1186/1471-2350-14-123

 received in 2013-03-28, accepted in 2013-11-25,  发布年份 2013

【 摘 要 】

Background

Variants in the FTO gene have been associated with obesity in children, but this association has not been shown with other biomarkers. We assessed the association of 52 FTO polymorphisms, spanning the whole gene, with obesity and estimated the influence of these polymorphisms on anthropometric, clinical and metabolic parameters as well as inflammation and cardiovascular disease (CVD) risk biomarkers among Spanish children.

Methods

A multicentre case–control study was conducted in 534 children (292 obese and 242 with normal-BMI). Anthropometric, clinical, metabolic, inflammation and CVD risk markers were compared using the Student’s t-test for unpaired samples. The genotype relative risk was assessed by comparing the obese and normal-BMI group, calculating the odds ratio. The association of each SNP with phenotypic parameters was analysed using either logistic or linear regression analysis.

Results

All anthropometric, clinical and metabolic factors as well as inflammatory and CVD risk biomarkers were higher in the obese than in the normal-BMI group, except adiponectin and HDL-c that were lower, and glucose, LDL-c, and metalloproteinase-9 that did not show difference. Four polymorphisms (rs9935401, rs9939609, rs9928094 and rs9930333) were positively associated with obesity and in linkage disequilibrium between each other; the haplotype including the risk alleles of these polymorphisms showed a high risk for obesity. The rs8061518 was negatively associated with obesity and the haplotype including this SNP and rs3826169, rs17818902 and rs7190053 showed a decreased risk for obesity. Additionally, the rs8061518 was associated with weight, diastolic blood pressure, insulin, homeostatic model assessment of insulin resistance, leptin, and active plasminogen inhibitor activator-1 after sex and age adjustment; however, after an additional BMI adjustment, this polymorphism remained associated only with leptin.

Conclusions

We validated the previous reported association of genetic variability in intron 1 of the FTO gene with the risk of obesity and found no association with other related traits in this region of the gene. We have observed strong statistical evidence for an association of rs8061518 in intron 3 of the gene with decreased risk of obesity and low concentration of leptin.

【 授权许可】

   
2013 Olza et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

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