Genotypic carriers of the obesity-associated FTO polymorphism exhibit different cardiometabolic profiles after an intervention

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Abstract

ABSTRACT Background: Children and adolescents with at-risk genotypes (AA/AT) of the rs9939609 polymorphism in FTO, a fat mass and obesity-associated gene, may exhibit different cardiometabolic profile responses than subjects with the TT genotype after an interdisciplinary intervention. Methods: The sample consisted of 36 school children from southern Brazil. We used DNA quantitation and real-time polymerase chain reaction (PCR) for polymorphism genotyping. We measured anthropometric parameters (body mass index (BMI), waist circumference, hip circumference, waist-hip ratio, body fat percentage and skinfold sum), biochemical parameters (glucose, lipid profile, ultra-sensitive C-reactive protein, uric acid, alanine aminotransferase, aspartate aminotransferase, insulin and adiponectin) and blood pressure. The 4-month intervention consisted of physical education classes, nutritional counseling, and postural and oral health counseling. Results: We observed no significant differences among the groups (AA, AT and TT) after the intervention. However, we observed improvements in three parameters (waist circumference, hip circumference and C-reactive protein) in the AT/AA genotype group and in two parameters (hip circumference and uric acid) in the TT genotype group. Conclusions: After an intervention program, carriers of at-risk genotypes for obesity (AA/AT) do not exhibit differences in biochemical parameters, blood pressure and anthropometric parameters compared with carriers of the TT genotype.

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VI Diretrizes Brasileiras de Hipertensão

(2010)

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FTO genotype is associated with body mass index after the age of seven years but not with energy intake or leisure-time physical activity.

Maarit Hakanen, Olli Simell, Terho Lehtimäki … (2009)

A common variant in the FTO gene, rs9939609, associates with body mass index (BMI) in adults and in children aged 7 yr or older. Our aim was to examine the associations of the FTO genotype with BMI, cardiovascular risk factors, energy intake, and leisure-time physical activity in children followed up since infancy. Healthy participants of the STRIP Study, genotyped for rs9939609, were followed from age 7 months (n = 640) to 15 yr (n = 438). The children were randomly assigned to lifestyle intervention and control groups. Height, weight, blood pressure, and serum lipids were measured annually. Food records and physical activity index were obtained at age 15 yr. The FTO genotype did not associate with BMI in children younger than 7 yr of age. From age 7 yr onward, the children homozygous for the A allele had progressively higher BMI than the children with one or two T alleles (P = 0.029 for FTO by age interaction). Furthermore, in longitudinal, BMI Z-score-adjusted analysis, the AA genotype associated with higher systolic and diastolic blood pressure and with elevated serum total and low-density lipoprotein-cholesterol (P = 0.01, P < 0.001, P = 0.05, and P = 0.04 for main effect, respectively). The FTO genotype did not associate with energy intake or physical activity index at age 15. The FTO *Study group interactions were not significant. Our results suggest that the effect of the FTO genotype on BMI becomes evident only after age 7 yr. These results further suggest that the FTO gene is not directly associated with energy intake or physical activity.

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Genetic Predictors of Weight Loss and Weight Regain After Intensive Lifestyle Modification, Metformin Treatment, or Standard Care in the Diabetes Prevention Program

Linda M Delahanty, Qing-Qing Pan, Kathleen A Jablonski … (2012)

OBJECTIVE We tested genetic associations with weight loss and weight regain in the Diabetes Prevention Program, a randomized controlled trial of weight loss–inducing interventions (lifestyle and metformin) versus placebo. RESEARCH DESIGN AND METHODS Sixteen obesity-predisposing single nucleotide polymorphisms (SNPs) were tested for association with short-term (baseline to 6 months) and long-term (baseline to 2 years) weight loss and weight regain (6 months to study end). RESULTS Irrespective of treatment, the Ala12 allele at PPARG associated with short- and long-term weight loss (−0.63 and −0.93 kg/allele, P ≤ 0.005, respectively). Gene–treatment interactions were observed for short-term (LYPLAL1 rs2605100, Plifestyle*SNP = 0.032; GNPDA2 rs10938397, Plifestyle*SNP = 0.016; MTCH2 rs10838738, Plifestyle*SNP = 0.022) and long-term (NEGR1 rs2815752, Pmetformin*SNP = 0.028; FTO rs9939609, Plifestyle*SNP = 0.044) weight loss. Three of 16 SNPs were associated with weight regain (NEGR1 rs2815752, BDNF rs6265, PPARG rs1801282), irrespective of treatment. TMEM18 rs6548238 and KTCD15 rs29941 showed treatment-specific effects (Plifestyle*SNP < 0.05). CONCLUSIONS Genetic information may help identify people who require additional support to maintain reduced weight after clinical intervention.