ABCA1 Gene Variant is Associated with Early-Onset Type 2 Diabetes in the Mexican Population

¹MT Villarreal-Molina, ¹C Aguilar-Salinas, ¹O Arellano-Ocampos, ¹MT Flores-Dorantes, ¹M Villalobos-Comparán, ²R Ramírez-Campuzano, ²R Sandoval-Silva, ¹FJ Gómez-Pérez, ³M Königsberg-Fainstein, ⁴M Menjívar, ¹MT Tusié-Luna, ¹S Canizales-Quinteros
¹Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Vasco de Quiroga No. 15 Col. Sección XVI, México, D. F. 14000, Mexico, ²Instituto de Seguridad y Servicios Sociales de los Trabajadores del Estado, Subdirección Médica, México, D. F., Mexico, ³Universidad Autónoma Metropolitana-Iztapalapa, División de Ciencias Biológicas y de la Salud, México, D. F., Mexico, ⁴Universidad Nacional Autónoma de México, Facultad de Química, México, D. F., Mexico

The ATP binding cassette transporter 1 (ABCA1) is well known for its role in cholesterol efflux and HDL formation. In the mouse model, it was recently found that ABCA1 also plays a critical role in beta-cell cholesterol homeostasis and is required for insulin secretion, establishing a new role for ABCA1 in beta-cell cholesterol metabolism and glucose homeostasis. We previously reported a highly frequent non-synonymous ABCA1 variant (R230C) which was significantly associated with low HDL-C levels, obesity and the metabolic syndrome in the Mexican-Mestizos. We thus investigated whether this variant is associated with type 2 diabetes (T2D) in this population. The study included 247 T2D individuals and 211 non-T2D individuals aged > 50 years. Overall, the R230C variant was significantly associated with T2D [OR 2.13 (95% CI 1.30-3.52), P=0.002]. However, this association was more significant in individuals with early-onset T2D (onset before age 45; n=77) [OR 3.84, 95% CI 2.11-6.99; p< 0.00001), and not significant in late-onset T2D individuals (n=170; p=0.472). The association with early-onset diabetes suggests an insulin secretion defect. Because of the high frequency of the R230C variant in the Mexican population, it is necessary to assess the functional consequences of this variant, as well as the response of carriers to diet and pharmacological treatment.