The FOXC2 -512C>T variant is associated with hypertriglyceridaemia and increased serum C-peptide in Danish Caucasian glucose-tolerant subjects.

Aims/hypothesis: The transcription factor FOXC2 plays a key role in adipocyte differentiation and the FOXC2 gene is a candidate gene for Type 2 diabetes, obesity and dyslipidaemia. We investigated whether the FOXC2 -512C>T promoter variant is associated with Type 2 diabetes or its intermediary phenotypes in glucose tolerant subjects.

Methods: The variant was genotyped using PCR-RFLP in 705 unrelated Type 2 diabetic patients, 505 unrelated glucose-tolerant control subjects and 219 glucose-tolerant offspring of Type 2 diabetic probands.

Results: The frequency of the T-allele was 58% (95% CI 56-61%) and 59% (56-62%) among the Type 2 diabetic patients and the unrelated glucose-tolerant control subjects, respectively ( p=0.6). Among the glucose-tolerant subjects, the T-allele carriers had higher fasting serum triglyceride ( p=0.03), fasting serum C-peptide concentrations ( p=0.009) and insulinogenic index ( p=0.04). Furthermore, in glucose-tolerant women, the waist-to-hip ratio was significantly higher in carriers of the T-allele.

Conclusion/interpretation: Our data suggest that the FOXC2 -512C>T variant is not associated with Type 2 diabetes. However, among glucose-tolerant subjects the variant is associated with hypertriglyceridaemia and increased fasting serum C-peptide.