Abstract
BackgroundSeveral studies have reported an association between single nucleotide polymorphisms in the first intron of the FTO gene and body mass index (BMI) or obesity. However, this association has not yet been studied among the Portuguese population. This study aims to assess the association of three FTO polymorphisms (rs1861868, rs1421085 and rs9939609) with obesity-related outcomes in a sample of Portuguese children.MethodsWe examined a total of 730 children, 256 normal-weight (55.9% girls), 320 overweight (45.3% girls) and 154 obese (53.2% girls), aging from 6 to 12-years-old, recruited randomly from public schools in the central region of Portugal. DNA samples were genotyped for the three polymorphisms by allelic discrimination TaqMan assay. Association of the FTO polymorphisms with several anthropometric traits was investigated. Additionally, we tested association with the risk of obesity using overweight and obese vs. normal-weight children.ResultsWe found significant associations of rs9939609 and rs1421085 polymorphisms with weight, BMI, BMI Z-score, waist circumference and hip circumference, even after age and gender adjustment (p<0.05 in all traits). For rs1861868 polymorphism, marginally significant associations were obtained with weight (p = 0.081) and BMI (p = 0.096) after adjustment for age and gender. In case-control studies, both rs9939609 and rs1421085 polymorphisms were significantly associated with obesity (OR 1.97; 95% CI, 1.08–3.59; p = 0.026; OR 2.11; 95% CI, 1.17–3.81; p = 0.013, respectively) but not with overweight (p>0.05). Haplotype analyses identified two combinations (ACA and GCA) associated with a higher risk of obesity (OR 1.53; 95% CI, 1.06–2.22; p = 0.023; OR 1.73; 95% CI, 1.06–2.87; p = 0.030, respectively).ConclusionsThis study provides the first evidence for the association of FTO polymorphisms with anthropometric traits and risk of obesity in Portuguese children.
Highlights
Overweight and obesity are a major health issue associated with risk factors for the development of hypertension, type 2 diabetes and cardiovascular diseases [1]
The analysed children were divided into three groups according to the definition of body mass index (BMI) specified by International Obesity Task Force (IOTF) cut-offs [20]
From a total of 1433 children measured for anthropometric traits, genotyping was performed in a total of 730 children comprising 320 subjects classified as overweight ($25 kg/m2 BMI,30 kg/ m2), 154 classified as obese (BMI $30 kg/m2) and a control group of 256 subjects randomly selected from the total normal weight children (N = 959, BMI,25 kg/m2)
Summary
Overweight and obesity are a major health issue associated with risk factors for the development of hypertension, type 2 diabetes and cardiovascular diseases [1] This complex phenotype results from the interaction of environmental and multiple genetic factors influencing body mass index (BMI), with heritability estimated at 40–70% [2]. In 2007, a strong association was detected between common single nucleotide polymorphisms (SNPs) in the first intron of the fat mass and obesity-associated gene (FTO), on the chromosome 16q12.2, and risk of obesity [5,6] Of those SNPs, the rs9939609 is one of the most extensively studied, explaining about 1% of BMI heritability [5]. This study aims to assess the association of three FTO polymorphisms (rs1861868, rs1421085 and rs9939609) with obesity-related outcomes in a sample of Portuguese children
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