Volume 46, Number 11, 1576-1580, DOI: 10.1007/s00125-003-1213-6

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European Association for the Study of Diabetes

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

K. Yanagisawa, L. Hingstrup Larsen, G. Andersen, T. Drivsholm, A. Cederberg, R. Westergren, K. Borch-Johnsen, O. Pedersen, S. Enerbäck and T. Hansen

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Abstract

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.

Keywords  FOXC2 - genetics - single nucleotide polymorphism - Type 2 diabetes - hypertriglyceridaemia - association study

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