1. ¹Unit of Molecular Biology and Genomic Medicine, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Instituto de Investigaciones Biomédicas de la Universidad Nacional Autónoma de México, Mexico City, Mexico
2. ²Unit of Medical Research in Nutrition, Hospital de Pediatría, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Mexico City, Mexico
3. ³Department of Endocrinology and Metabolism, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico
4. ⁴Department of Human Genetics, David Geffen School of Medicine at UCLA, University of California Los Angeles, Los Angeles, California, USA
5. ⁵Faculty of Chemical and Biological Science, Universidad Autónoma de Sinaloa, Culiacán, Mexico
6. ⁶Department of Gastroenterology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico
7. ⁷Centre National de la Recherche Scientifique 8090, Institute of Biology, Pasteur Institute, Lille, France
8. ⁸Department of Biology, Facultad de Química, Universidad Nacional Autónoma de México, Mexico City, Mexico
9. ⁹Unit of Medical Research in Human Genetics, Hospital de Pediatría, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Mexico City, Mexico
10. ¹⁰Department of Biology of Reproduction, Hospital de Ginecología y Obstetricia # 3, Centro Médico Nacional La Raza, Instituto Mexicano del Seguro Social, Mexico City, Mexico
11. ¹¹Molecular Genetics Laboratory, Escuela Nacional de Antropología e Historia, Instituto Nacional de Antropologia e Historia, Mexico City, Mexico
12. ¹²National Coordination of Genomic Medicine, Instituto de Seguridad y Servicios Sociales de los Trabajadores del Estado, Mexico City, Mexico

Correspondence: Samuel Canizales-Quinteros (cani@servidor.unam.mx)

Received 10 February 2008; Accepted 30 May 2008; Published online 31 July 2008.

Abstract

Common polymorphisms in the fat mass and obesity-associated gene (FTO) have shown strong association with obesity in several populations. In the present study, we explored the association of FTO gene polymorphisms with obesity and other biochemical parameters in the Mexican population. We also assessed FTO gene expression levels in adipose tissue of obese and nonobese individuals. The study comprised 788 unrelated Mexican-Mestizo individuals and 31 subcutaneous fat tissue biopsies from lean and obese women. FTO single-nucleotide polymorphisms (SNPs) rs9939609, rs1421085, and rs17817449 were associated with obesity, particularly with class III obesity, under both additive and dominant models (P = 0.0000004 and 0.000008, respectively). These associations remained significant after adjusting for admixture (P = 0.000003 and 0.00009, respectively). Moreover, risk alleles showed a nominal association with lower insulin levels and homeostasis model assessment of B-cell function (HOMA-B), and with higher homeostasis model assessment of insulin sensitivity (HOMA-S) only in nonobese individuals (P _dom = 0.031, 0.023, and 0.049, respectively). FTO mRNA levels were significantly higher in subcutaneous fat tissue of class III obese individuals than in lean individuals (P = 0.043). Risk alleles were significantly associated with higher FTO expression in the class III obesity group (P = 0.047). In conclusion, FTO is a major risk factor for obesity (particularly class III) in the Mexican-Mestizo population, and is upregulated in subcutaneous fat tissue of obese individuals.