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The ABCA1 R230C Variant Affects HDL-cholesterol Levels and Body Mass Index in the Mexican Population: Association with Obesity and Obesity-Related Comorbidities

¹Unit of Molecular Biology and Genomic Medicine, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán (INCMNSZ), Instituto de Investigaciones Biomédicas de la Universidad Nacional Autónoma de México, Mexico City, Mexico
²PhD program in Experimental Biology, Universidad Autónoma Metropolitana, Mexico City, Mexico
³Department of Endocrinology and Metabolism, INCMNSZ, Mexico City, Mexico
⁴Unit of Medical Research in Nutrition, Hospital de Pediatría, Centro Médico Nacional Siglo XXI-IMSS, Mexico City, Mexico
⁵Unit of Medical Research in Human Genetics, Hospital de Pediatría, Centro Médico Nacional, Siglo XXI-IMSS, Mexico City, Mexico
⁶Department of Biology, Facultad de Química, Universidad Nacional Autónoma de México, Mexico City, Mexico
⁷Department of Genetics, Instituto Nacional de Neurología y Neurociencias "Manuel Velasco Suarez", Mexico City, Mexico
⁸Division of Health and Biological Sciences, Universidad Autónoma Metropolitana-Iztapalapa, Mexico City, Mexico
⁹National Coordination of Genomic Medicine, Instituto de Seguridad y Servicios Sociales de los Trabajadores del Estado, Mexico City, Mexico

Correspondence: cani{at}servidor.unam.mx

Although the ATP binding cassette transporter 1 (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-C levels to seek functional variants. A highly frequent non-synonymous variant (R230C) was identified in low HDL-C but not in high HDL-C 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 was found in 20.1% of these individuals. The variant was significantly associated not only with decreased HDL-C and Apo A-I levels, but also with obesity (OR=2.527; P=0.005), the metabolic syndrome (OR=1.893; P=0.0007) and type 2 diabetes (OR=4.527; P=0.003). All these associations remained significant after adjusting for admixture (P=0.011, P=0.001, P=0.006, respectively). This is the first study reporting the association of an ABCA1 variant with obesity and obesity-related comorbidities, 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]