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

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, Mexico
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

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 x 10^–6). Both associations remained significant after adjusting for admixture (P=0.0008 and P=8.1 x 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 x 10^–6 and 9.4 x 10^–8, respectively).

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

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