[Association of FTO gene polymorphisms and morbid obesity in the population of Extremadura (Spain)]. / Asociación de polimorfismos en el gen FTO con la obesidad mórbida en la población extremeña.

OBJECTIVE: To select individuals whose morbid obesity can be attributed mainly to their individual genetic profile. After excluding patients with potential monogenic syndromes or diseases associated with obesity, we evaluated the association of the single nucleotide polymorphisms (SNPs) rs1861868 and rs9939609 of the fat-mass and obesity-associated FTO gene with an inherited predisposition to morbid obesity. PATIENTS AND METHODS: We evaluated 270 patients with morbid obesity and onset before the age of 14 years and selected 194 due to their phenotypes and family history; 289 control individuals were included. The rs1861868 and rs9939609 variants, located in the FTO gene, were genotyped. Genotype and haplotype frequencies were compared between cases and controls. RESULTS: The A allele of rs9939609 was associated with severe obesity starting in childhood among the Spanish population. The rs1861868 G/rs9939609 A haplotype of the FTO gene was also significantly associated with severe obesity in our population, with an odds ratio of 3.03 (95% confidence interval, 1.74-5.27). CONCLUSION: Analysis of the genetic basis of obesity requires rigorous selection of cases. In this study, the association of the rs9939609 SNP with obesity widely described in distinct populations was confirmed among overweight Spanish children. Genotyping rs1861868 allowed us to identify the first risk haplotype in the FTO gene, which is located in the adjacent haplotype block containing rs9939609. In-depth study of the variability of the FTO gene is essential to define its deleterious capacity.

FTO risk haplotype among early onset and severe obesity cases in a population of western Spain.

Childhood and adult obesity have been widely associated with FTO genetic variability in different populations. This study aimed to investigate the linkage disequilibrium (LD) block structure of a region surrounding the candidate rs9939609 SNP and determine the best single nucleotide polymorphism (SNP) combination that explains the higher proportion of variability observed in children with severe obesity, including obese subjects from families with a very high occurrence of obesity. A sliding window approach pointed to a block containing the rs1477196/rs17817449/rs9939609 haplotype (P value 3.1 × 10(-8)). Carriers of the GGA combination had an increased risk of obesity (odds ratio (OR) 2.07, 95% confidence interval (CI) 1.41-3.04, P = 2.0 × 10(-4)) with respect to those individuals with the reference ATT haplotype. A further SNP, rs9921255, also showed association with obesity (P = 8.3 × 10(-4), OR 1.77; 95% CI 1.15-2.74 and OR 5.78; 95% CI 1.22-27.49 for heterozygotes and homozygotes, respectively) and did not segregate with the previously described risk haplotype. The calculation of risk score based on the GGA haplotype combined with the rs9921255 variant showed a much greater effect of the FTO gene on high BMI. This score yields an attributable risk of 34% for severe obesity, and the increased risk per risk allele was 1.71 (P = 1.0 × 10(-6)). We conclude that the description of this polymorphic combination in the FTO gene could be useful for the early identification of inherited susceptibility to weight-gain since childhood, with a higher sensitivity than considering the effect of a single marker.

Asociación de polimorfismos en el gen FTO con la obesidad mórbida en la población extremeña / Association of FTO gene polymorphisms and morbid obesity in the population of Extremadura (Spain)

ObjetivoSeleccionar individuos cuya obesidad mórbida (OM) se pueda atribuir preferentemente al perfil genético individual. Tras descartar pacientes con posibles síndromes monogénicos y otras enfermedades con obesidad asociada, evaluar la asociación de la variabilidad del gen FTO (asociado con la masa grasa y la obesidad), sobre la base de los polimorfismos de un solo nucleótido (SNP) con rs1861868 y rs9939609, con la predisposición heredada a padecer OM.Pacientes y métodosTras evaluar a 270 pacientes con OM instaurada antes de los 14 años, seleccionamos a 194 por su fenotipo y la historia familiar referida; se incluyó a 289 individuos controles. Se genotiparon los cambios en el SNP rs1861868 y rs9939609 del gen FTO, y comparamos sus frecuencias genotípicas y haplotípicas en ambos grupos poblacionales.ResultadosSe confirmó la asociación del alelo A del SNP rs9939609 con la obesidad grave instaurada en la infancia en la población española. Los individuos portadores del haplotipo rs1861868 G/rs9939609 A del gen FTO mostraron un incremento del riesgo (odds ratio de 3,03; intervalo de confianza del 95%: 1,74–5,27) a padecer obesidad mórbida en nuestra población.ConclusiónAnalizar las bases genéticas de la obesidad precisa una rigurosa selección de los casos. La asociación del SNP rs9939609 con la obesidad, ampliamente descrita en distintas poblaciones, se confirma en la población española. Identificamos el primer haplotipo de riesgo al analizar el SNP rs1861868 del bloque haplotípico contiguo al que contiene el primero. Es preciso estudiar en profundidad la variabilidad interindividual del gen FTO para identificar la causa de su capacidad deletérea a la enfermedad (AU)

ObjectiveTo select individuals whose morbid obesity can be attributed mainly to their individual genetic profile. After excluding patients with potential monogenic syndromes or diseases associated with obesity, we evaluated the association of the single nucleotide polymorphisms (SNPs) rs1861868 and rs9939609 of the fat-mass and obesity-associated FTO gene with an inherited predisposition to morbid obesity.Patients and methodsWe evaluated 270 patients with morbid obesity and onset before the age of 14 years and selected 194 due to their phenotypes and family history; 289 control individuals were included. The rs1861868 and rs9939609 variants, located in the FTO gene, were genotyped. Genotype and haplotype frequencies were compared between cases and controls.ResultsThe A allele of rs9939609 was associated with severe obesity starting in childhood among the Spanish population. The rs1861868 G/rs9939609 A haplotype of the FTO gene was also significantly associated with severe obesity in our population, with an odds ratio of 3.03 (95% confidence interval, 1.74–5.27).ConclusionAnalysis of the genetic basis of obesity requires rigorous selection of cases. In this study, the association of the rs9939609 SNP with obesity widely described in distinct populations was confirmed among overweight Spanish children. Genotyping rs1861868 allowed us to identify the first risk haplotype in the FTO gene, which is located in the adjacent haplotype block containing rs9939609. In-depth study of the variability of the FTO gene is essential to define its deleterious capacity (AU)