ABC Transporter Genes and Risk of Type 2 Diabetes A study of 40,000 individuals from the general population

作者：Schou Jesper; Tybjaerg Hansen Anne; Moller Holger J; Nordestgaard Borge G; Frikke Schmidt Ruth^*

来源：Diabetes Care, 2012, 35(12): 2600-2606.

DOI：10.2337/dc12-0082

OBJECTIVE-Alterations of pancreatic beta-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. %26lt;br%26gt;RESEARCH DESIGN AND METHODS-We 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%26gt;T) (n = 322) and a common variant (ABCG1 g.-530A%26gt;G) were further genotyped in the Copenhagen General Population Study (CGPS) (n = 30,415). %26lt;br%26gt;RESULTS-Only one of the variants examined, ABCG1 g.-530A%26gt;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%26gt;T) nor ABCG1 g.-530A%26gt;G were associated with type 2 diabetes (P values %26gt;0.57 and %26gt;0.30, respectively). %26lt;br%26gt;CONCLUSIONS-Genetic variations in ABCA1 and ABCG1 were not associated with increased risk of type 2 diabetes in the general population. These data were obtained in general population samples harboring the largest number of heterozygotes for loss-of-function mutations in ABCA1 and ABCG1.

• 出版日期2012-12