Association of the ATP-Binding Cassette Transporter A1 R230C Variant With Early-Onset Type 2 Diabetes in a Mexican Population
- M. Teresa Villarreal-Molina1,
- M. Teresa Flores-Dorantes1,
- Olimpia Arellano-Campos2,
- Marisela Villalobos-Comparan1,
- Maricela Rodríguez-Cruz3,
- Angel Miliar-García4,
- Adriana Huertas-Vazquez1,
- Marta Menjivar5,
- Sandra Romero-Hidalgo6,
- Niels H. Wacher7,
- M. Teresa Tusie-Luna1,
- Miguel Cruz7,
- Carlos A. Aguilar-Salinas2,
- Samuel Canizales-Quinteros1 and
- the Metabolic Study Group
- 1Unit 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
- 2Department of Endocrinology and Metabolism, INCMNSZ, Mexico City, Mexico
- 3Unit of Medical Research in Nutrition, Pediatrics Hospital, National Medical Center XXI Century, Mexican Institute of Social Security, Mexico City, Mexic
- 4Postgraduate Studies and Research Section, Postgraduate Studies and Research Section, School of Medicine, National Polytechnic Institute, Mexico City, Mexico
- 5Department of Biology, Faculty of Chemistry, National Autonomous University of Mexico, Mexico City, Mexico
- 6National Coordination of Genetic Medicine, Institute of Social Security and Services for Government Employees, Mexico City, Mexico
- 7Units 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 242 type 2 diabetic case subjects and 225 control subjects with similar characteristics.
RESULTS—R230C/C230C genotypes were significantly more frequent in type 2 diabetic individuals (24.6%) than in control subjects (11.4%) in the initial study group (OR 2.501; P = 0.001). After stratifying by age at diagnosis, the association was significant only in the early-onset group (age at diagnosis ≤45 years) (OR 3.776, P = 3.3 × 10−6). Both associations remained significant after adjusting for admixture (P = 0.0008 and P = 8.1 × 10−6, respectively). Similar trends were observed in the independent study group, and the combined analysis of both populations showed a highly significant association of the R230C variant with type 2 diabetes, particularly with that of early onset (P = 7.6 × 10−6 and 9.4 × 10−8, respectively).
CONCLUSIONS—The R230C ABCA1 variant is associated with type 2 diabetes, particularly of early onset, in the Mexican-Mestizo population.
- ABCA1, ATP-binding cassette transporter A1
- AIM, ancestry informative marker
- Apo A-I, apolipoprotein A-I
- LD, linkage disequilibrium
- SNP, single nucleotide polymorphism
Footnotes
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M.T.V.-M. is currently affiliated with the National Institute of Genomic Medicine.
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Published ahead of print at http://diabetes.diabetesjournals.org on 14 November 2007. DOI: 10.2337/db07-0484.
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Additional information for this article can be found in an online appendix at http://dx.doi.org/10.2337/db07-0484.
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M.T.V.-M. and M.T.F.-D. contributed equally to this work.
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A complete list of individuals and institutions participating in the Metabolic Study Group appears in the appendix.
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- Accepted November 7, 2007.
- Received April 6, 2007.
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