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

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.