ABCMdb

PMID: 23139370

Schou J, Tybjaerg-Hansen A, Moller HJ, Nordestgaard BG, Frikke-Schmidt R
ABC transporter genes and risk of type 2 diabetes: a study of 40,000 individuals from the general population.
Diabetes Care. 2012 Dec;35(12):2600-6. doi: 10.2337/dc12-0082. Epub 2012 Nov 8., [PubMed]

Sentences

No. Mutations Sentence Comment

5 ABCA1 p.Asn1800His 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). Login to comment 7 ABCA1 p.Asn1800His 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 2 diabetes (P values .0.57 and .0.30, respectively). Login to comment 17 ABCA1 p.Asn1800His Finally, we recently reported that two functional variants, ABCA1 N1800H and ABCG1 g.-376C.T, were associated with, respectively, substantial reductions in levels of HDL cholesterol or reduced ABCG1 mRNA expression levels and increased risk of ischemic heart disease and myocardial infarction (12,13)drisk factors and disease entities closely related to diabetes. Login to comment 45 ABCA1 p.Asn1800His Two loss-of-function mutations (ABCA1 N1800H and ABCG1 g.-376C.T), as well as a common variant associated with reduced risk of type 2 diabetes in the CCHS (ABCG1 g.-530A.G), were further genotyped in the CGPS. Login to comment 85 ABCA1 p.Asn1800His Two loss-of-function mutations, as well as a common variant with effect on risk of type 2 diabetes in the CCHS, were further genotyped in the CGPS and displayed minor allele frequencies similar to those in the CCHS: 0.1, 0.2, and 6.7% for ABCA1 N1800H, ABCG1 g.- 376C.T, and ABCG1 g.-530A.G, respectively. Login to comment 86 ABCA1 p.Glu1172Asp Genotype frequencies did not differ from those predicted by Hardy-Weinberg equilibrium (P values 0.11-0.98), except for ABCA1 E1172D (P = 0.03), in the CCHS. Login to comment 89 ABCA1 p.Asn1800His After application of a Bonferroni-corrected P value of 0.0002 (0.05/8 biochemical markers multiplied by 27 genetic variants), only one association remained significant: plasma levels of HDL cholesterol were reduced by 0.45 mmol/L in heterozygotes for ABCA1 N1800H compared with noncarriers (P 5 0.0001) (Fig. 1); the corresponding reduction for apoAI was 27.6 mg/dL. Login to comment 97 ABCA1 p.Asn1800His ABCA1 p.Asn1800His Neither the two loss-of-function mutations nor the ABCG1 g.- 530A.G associated with type 2 diabetes in the CGPS (ABCA1 N1800H AC vs. AA odds ratio 0.7 [95% CI 0.2-2.8], ABCG1 g.- 376C.T CT vs. CC 1.1 [0.5-2.3], ABCG1 g.-530A.G AG vs. AA 1.1 [0.9-1.3], and GG vs. AA 0.8 [0.3-2.2]) or in CCHS and CGPS combined (N1800H AC vs. AA 0.6 [0.2-1.8], g.-376C.T CT vs. CC 1.0 [0.5-1.8], g.-530A.G AG vs. AA 1.0 [0.8-1.1], and GG vs. AA 1.1 [0.5-2.0]) (Fig. 4). Login to comment 98 ABCA1 p.Asn1800His Finally, when burden testing of rare variants was performed, neither collapsed genotypes including all rare variants with minor allele frequencies ,1% (CCHS: P = 0.34) nor collapsed genotypes including rare variants that were experimentally verified to be functional (ABCA1 N1800H and ABCG1 g.-376C.T) associated with type 2 diabetes (CCHS and CGPS combined: P = 0.70). Login to comment 102 ABCA1 p.Asn1800His This is the largest study to date of genetic variation in ABCA1 and ABCG1 and risk of type 2 diabetes and, in particular, is the largest study of loss-of-function mutations, including 94 ABCA1 N1800H heterozygotes and 228 ABCG1 g.-376C.T heterozygotes. Login to comment 107 ABCA1 p.Arg230Cys In a case-control study of 244 patients with type 2 diabetes versus 202 nondiabetic control subjects, ABCA1 R230C was reported to associate with type 2 diabetes in a Mexican-Mestizo population (9). Login to comment