Association of the ATP-binding cassette transporter A1 R230C variant with early-onset type 2 diabetes in a Mexican population.
OBJECTIVE
The ATP-binding cassette transporter A1 (ABCA1) R230C variant is associated with low HDL cholesterol 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.


METHODS
The initial group included 446 unrelated Mexican individuals: 244 with type 2 diabetes aged 20-69 years (121 with onset </=45 years), and 202 nondiabetic control subjects aged >50 years. An independent study group included 242 type 2 diabetic case subjects and 225 control subjects with similar characteristics.


RESULTS
R230C/C230C genotypes were significantly more frequent in type 2 diabetic individuals (24.6%) than in control subjects (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).


CONCLUSIONS
The R230C ABCA1 variant is associated with type 2 diabetes, particularly of early onset, in the Mexican-Mestizo population.
Villarreal-Molina
M Teresa
MT
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.
Flores-Dorantes
M Teresa
MT
Arellano-Campos
Olimpia
O
Villalobos-Comparan
Marisela
M
Rodríguez-Cruz
Maricela
M
Miliar-García
Angel
A
Huertas-Vazquez
Adriana
A
Menjivar
Marta
M
Romero-Hidalgo
Sandra
S
Wacher
Niels H
NH
Tusie-Luna
M Teresa
MT
Cruz
Miguel
M
Aguilar-Salinas
Carlos A
CA
Canizales-Quinteros
Samuel
S
D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters / Q000235:genetics*; D000328:Adult; D017668:Age of Onset; D000368:Aged; D000369:Aged, 80 and over; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics*; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D008800:Mexico; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012016:Reference Values
C577836:ABCA1 protein, human; D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters