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The ATP-Binding Cassette Transporter A1 R230C Variant Affects HDL Cholesterol Levels and BMI in the Mexican Population

Association With Obesity and Obesity-Related Comorbidities

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 PhD Program in Experimental Biology, Autonomous Metropolitan University, Mexico City, Mexico
³ Department of Endocrinology and Metabolism, INCMNSZ, Institute of Biomedical Research, National Autonomous University of Mexico, Mexico City, Mexico
⁴ Unit of Medical Research in Nutrition, Pediatrics Hospital, National Medical Center XXI Century, Mexican Institute of Social Security, Mexico City, Mexico
⁵ Unit of Medical Research in Human Genetics, Pediatrics Hospital, National Medical Center XXI Century, Mexican Institute of Social Security, Mexico City, Mexico
⁶ Department of Biology, Faculty of Chemistry, National Autonomous University of Mexico, Mexico City, Mexico
⁷ Department of Geriatrics, Manuel Velasco Suarez National Institute of Neurology and Neurosurgery, Mexico City, Mexico
⁸ Division of Health and Biological Sciences, Autonomous Metropolitan University-Iztapalapa, Mexico City, Mexico
⁹ National Coordination of Genetic Medicine, Institute of Social Security and Services for Government Employees, 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

Abbreviations: ABCA1, ATP-binding cassette transporter A1; apo, apolipoprotein; ATP-III, National Cholesterol Education Program Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults, Adult Treatment Panel III; CHD, coronary heart disease; IDF, International Diabetes Federation; INCMNSZ, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán

Although ATP-binding cassette transporter A1 (ABCA1) is well known for its role in cholesterol efflux and HDL formation, it is expressed in various tissues, where it may have different functions. Because hypoalphalipoproteinemia is highly prevalent in Mexico, we screened the ABCA1 coding sequence in Mexican individuals with low and high HDL cholesterol levels to seek functional variants. A highly frequent nonsynonymous variant (R230C) was identified in low–HDL cholesterol but not in high–HDL cholesterol individuals (P = 0.00006). We thus assessed its frequency in the Mexican-Mestizo general population, seeking possible associations with several metabolic traits. R230C was screened in 429 Mexican Mestizos using Taqman assays, and it was found in 20.1% of these individuals. The variant was significantly associated not only with decreased HDL cholesterol and apolipoprotein A-I levels but also with obesity (odds ratio 2.527, P = 0.005), the metabolic syndrome (1.893, P = 0.0007), and type 2 diabetes (4.527, P = 0.003). All of these associations remained significant after adjusting for admixture (P = 0.011, P = 0.001, and P = 0.006, respectively). This is the first study reporting the association of an ABCA1 variant with obesity and obesity-related comorbidities as being epidemiologically relevant in the Mexican population.

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				M. T. Villarreal-Molina, M. T. Flores-Dorantes, O. Arellano-Campos, M. Villalobos-Comparan, M. Rodriguez-Cruz, A. Miliar-Garcia, A. Huertas-Vazquez, M. Menjivar, S. Romero-Hidalgo, N. H. Wacher, et al. Association of the ATP-Binding Cassette Transporter A1 R230C Variant With Early-Onset Type 2 Diabetes in a Mexican Population Diabetes, February 1, 2008; 57(2): 509 - 513. [Abstract] [Full Text] [PDF]