Dataset Information

ABC transporter genes and risk of type 2 diabetes: a study of 40,000 individuals from the general population.

ABSTRACT:

Objective

Alterations of pancreatic ?-cell cholesterol content may contribute to ?-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 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>T) (n = 322) and a common variant (ABCG1 g.-530A>G) were further genotyped in the Copenhagen General Population Study (CGPS) (n = 30,415).

Results

Only 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 2 diabetes (P values >0.57 and >0.30, respectively).

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.

SUBMITTER: Schou J

PROVIDER: S-EPMC3507608 | biostudies-literature | 2012 Dec

REPOSITORIES: biostudies-literature

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Publications

ABC transporter genes and risk of type 2 diabetes: a study of 40,000 individuals from the general population.

Schou Jesper J Tybjærg-Hansen Anne A Møller Holger J HJ Nordestgaard Børge G BG Frikke-Schmidt Ruth R

Diabetes care 20121108 12

<h4>Objective</h4>Alterations of pancreatic β-cell cholesterol content may contribute to β-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.<h4>Research design and methods</h4>We tested whether genetic variation in the promoter and coding regions of ABCA1 and ABCG1 predicted ...[more]

PMID: 23139370

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Dataset Information

ABC transporter genes and risk of type 2 diabetes: a study of 40,000 individuals from the general population.

Objective

Research design and methods

Results

Conclusions

Publications

ABC transporter genes and risk of type 2 diabetes: a study of 40,000 individuals from the general population.

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