Association of the ATP-binding cassette transporter A1 R230C Variant with Early-Onset Type 2 Diabetes in the Mexican Population

  1. M. Teresa Villarreal-Molina1,
  2. M. Teresa Flores-Dorantes1,
  3. Olimpia Arellano-Campos2,
  4. Marisela Villalobos-Comparan1,
  5. Maricela Rodríguez-Cruz3,
  6. Angel Miliar-García4,
  7. Adriana Huertas-Vazquez1,
  8. Marta Menjivar5,
  9. Sandra Romero-Hidalgo6,
  10. Niels H. Wacher7,
  11. M. Teresa Tusie-Luna1,
  12. Miguel Cruz7,
  13. Carlos A. Aguilar-Salinas2 and
  14. Samuel Canizales-Quinteros (cani{at}servidor.unam.mx)1 The Metabolic Study Group
  1. 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. 2 Department of Endocrinology and Metabolism, INCMNSZ, Mexico City, Mexico
  3. 3 Unit of Medical Research in Nutrition, Pediatrics Hospital, National Medical Center XXI Century, Mexican Institute of Social Security, Mexico City, Mexico
  4. 4 Postgraduate Studies and Research Section, Postgraduate Studies and Research Section, School of Medicine, National Polytechnic Institute, Mexico City, Mexico
  5. 5 Department of Biology, Faculty of Chemistry, National Autonomous University of Mexico, Mexico City, Mexico
  6. 6 National Coordination of Genetic Medicine, Institute of Social Security and Services for Government Employees, Mexico City, Mexico
  7. 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

    Abstract

    Objective: The ATP-binding cassette transporter A1 (ABCA1) R230C variant is associated with low high density lipoprotein-cholesterol (HDL-C) levels, obesity and the metabolic syndrome in Mexican-Mestizos. Because a pivotal role for ABCA1 in pancreatic beta-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 to 69 years (121 with onset ≤ 45 years), and 202 non-diabetic controls aged > 50 years. An independent study group included 242 type 2 diabetes cases and 225 controls with similar characteristics.

    Results: R230C/C230C genotypes were significantly more frequent in type 2 diabetic individuals (24.6%) than in controls (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).

    Conclusion: The R230C ABCA1 variant is associated with type 2 diabetes, particularly of early-onset in the Mexican-Mestizo population.

    Footnotes

      • Received April 6, 2007.
      • Accepted November 7, 2007.

    This Article

    1. Published online before print November 14, 2007, doi: 10.2337/db07-0484
    1. » Abstract
    2. Full Text (PDF)
    3. Online-Only Appendix
    4. All Versions of this Article:
      1. db07-0484v1
      2. 57/2/509most recent

    Current Issue

    1. December 2009, 58 (12)
      Current Issue
    1. Alert me to new issues of Diabetes