ABC Transporter Genes and Risk of Type 2 Diabetes

OBJECTIVEdAlterations of pancreatic b-cell cholesterol content may contribute to b-cell dysfunction. Two important determinants of intracellular cholesterol content are the ATP-binding cassette (ABC) transporters A1 (ABCA1) and-G1 (ABCG1). Whether genetic variation in ABCA1 and ABCG1 predicts risk of type 2 diabetes in the general population is unknown. RESEARCH DESIGN AND METHODSdWe tested whether genetic variation in the promoter and coding regions of ABCA1 and ABCG1 predicted risk of type 2 diabetes in the general population. Twenty-seven variants, identified by previous resequencing of both genes, were genotyped in the Copenhagen City Heart Study (CCHS) (n = 10,185). Two loss-of-function mutations (ABCA1 N1800H and ABCG1 g.-376C.T) (n = 322) and a common variant (ABCG1 g.-530A.G) were further genotyped in the Copenhagen General Population Study (CGPS) (n = 30,415). RESULTSdOnly one of the variants examined, ABCG1 g.-530A.G, predicted a decreased risk of type 2 diabetes in the CCHS (P for trend = 0.05). Furthermore, when validated in the CGPS or in the CCHS and CGPS combined (n = 40,600), neither the two loss-of-function mutations (ABCA1 N1800H, ABCG1 g.-376C.T) nor ABCG1 g.-530A.G were associated with type