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Diabetologia

Erschienen in:

01.11.2006 | Article

Polymorphisms in the gene encoding sterol regulatory element-binding factor-1c are associated with type 2 diabetes

verfasst von: A.-H. Harding, R. J. F. Loos, J. Luan, S. O’Rahilly, N. J. Wareham, I. Barroso

Erschienen in: Diabetologia | Ausgabe 11/2006

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Abstract

Aims/hypothesis

The sterol regulatory element-binding factor (SREBF)-1c is a transcription factor involved in the regulation of lipid and glucose metabolism. We have previously found evidence that a common SREBF1c single-nucleotide polymorphism (SNP), located between exons 18c and 19c, is associated with an increased risk of type 2 diabetes. The present study aimed to replicate our previously reported association in a larger case–control study and to examine an additional five SREBF1c SNPs for their association with diabetes risk and plasma glucose concentrations.

Methods

We genotyped six SREBF1c SNPs in two case–control studies (n=1,938) and in a large cohort study (n=1,721) and tested for association with type 2 diabetes and with plasma glucose concentrations (fasting and 120-min post-glucose load), respectively.

Results

In the case–control studies, carriers of the minor allele of the previously reported SNP (rs11868035) had a significantly increased diabetes risk (odds ratio [OR]=1.20 [95% CI 1.04–1.38], p=0.015). Also, three other SNPs (rs2236513, rs6502618 and rs1889018), located in the 5′ region, were significantly associated with diabetes risk (OR ≥1.21, p≤0.006). Furthermore, two SNPs (rs2236513 and rs1889018) in the 5′ region were weakly (p<0.09) associated with plasma glucose concentrations in the cohort study. Rare homozygotes had increased (p≤0.05) 120-min post-load glucose concentrations compared with carriers of the wild-type allele. Haplotype analyses showed significant (p=0.04) association with diabetes risk and confirmed the single SNP analyses.

Conclusions/interpretation

In summary, we replicated our previous finding and found evidence for SNPs in the 5′ region of the SREBF1c gene to be associated with the risk of type 2 diabetes and plasma glucose concentration.

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Titel: Polymorphisms in the gene encoding sterol regulatory element-binding factor-1c are associated with type 2 diabetes
verfasst von: A.-H. Harding
R. J. F. Loos
J. Luan
S. O’Rahilly
N. J. Wareham
I. Barroso
Publikationsdatum: 01.11.2006
Verlag: Springer-Verlag
Erschienen in: Diabetologia / Ausgabe 11/2006
Print ISSN: 0012-186X
Elektronische ISSN: 1432-0428
DOI: https://doi.org/10.1007/s00125-006-0430-1

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