Polymorphisms in the gene encoding sterol regulatory element-binding factor-1c are associated with type 2 diabetes.
OBJECTIVE
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 > or =1.21, p< or =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< or =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
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.
Harding
A-H
AH
MRC Epidemiology Unit, Cambridge, UK.
Loos
R J F
RJ
Luan
J
J
O'Rahilly
S
S
Wareham
N J
NJ
Barroso
I
I
D000368:Aged; D001786:Blood Glucose / Q000378:metabolism; D016022:Case-Control Studies; D015331:Cohort Studies; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000235:genetics*; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D051780:Sterol Regulatory Element Binding Protein 1 / Q000235:genetics*
D001786:Blood Glucose; D051780:Sterol Regulatory Element Binding Protein 1