Association of the ATP-Binding Cassette Transporter A1 R230C Variant With Early-Onset Type 2 Diabetes in a Mexican Population

Association of the ATP-Binding Cassette Transporter A1 R230C Variant With Early-Onset Type 2 Diabetes in a Mexican Population M. Teresa Villarreal-Molina 1 , M. Teresa Flores-Dorantes 1 , Olimpia Arellano-Campos 2 , Marisela Villalobos-Comparan 1 , Maricela Rodríguez-Cruz 3 , Angel Miliar-García 4 , Adriana Huertas-Vazquez 1 , Marta Menjivar 5 , Sandra Romero-Hidalgo 6 , Niels H. Wacher 7 , M. Teresa Tusie-Luna 1 , Miguel Cruz 7 , Carlos A. Aguilar-Salinas 2 , Samuel Canizales-Quinteros 1 and the Metabolic Study Group 1 Unit of Molecular Biology and Genomic Medicine, Salvador Zubiran National Institute of Medical Sciences and Nutrition (INCMNSZ), Institute of Biomedical Research, National Autonomous University of Mexico, Mexico City, Mexico 2 Department of Endocrinology and Metabolism, INCMNSZ, Mexico City, Mexico 3 Unit of Medical Research in Nutrition, Pediatrics Hospital, National Medical Center XXI Century, Mexican Institute of Social Security, Mexico City, Mexic 4 Postgraduate Studies and Research Section, Postgraduate Studies and Research Section, School of Medicine, National Polytechnic Institute, Mexico City, Mexico 5 Department of Biology, Faculty of Chemistry, National Autonomous University of Mexico, Mexico City, Mexico 6 National Coordination of Genetic Medicine, Institute of Social Security and Services for Government Employees, Mexico City, Mexico 7 Units of Medical Research in Clinical Epidemiology and Biochemistry, Specialties Hospital, National Medical Center XXI Century, Mexican Institute of Social Security, Mexico City, Mexico Address correspondence and reprint requests to Samuel Canizales-Quinteros, PhD, Unidad de Biología Molecular y Medicina Genómica, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Vasco de Quiroga #15 Colonia Sección 16, Tlalpan 14000, México D.F. E-mail: cani{at}servidor.unam.mx Abstract OBJECTIVE— The ATP-binding cassette transporter A1 (ABCA1) R230C variant is associated with low HDL cholesterol levels, obesity, and the metabolic syndrome in Mexican-Mestizos. Because a pivotal role for ABCA1 in pancreatic β-cell function was recently observed in the mouse model, we assessed the association of this variant with type 2 diabetes in this population. RESEARCH DESIGN AND METHODS— The initial group included 446 unrelated Mexican individuals: 244 with type 2 diabetes aged 20–69 years (121 with onset ≤45 years), and 202 nondiabetic control subjects aged >50 years. An independent study group included 24