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


CONCLUSIONS
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.
Yanagisawa
K
K
Steno Diabetes Center and Hagedorn Research Institute, Gentofte, Denmark. kyan@steno.dk
Hingstrup Larsen
L
L
Andersen
G
G
Drivsholm
T
T
Cederberg
A
A
Westergren
R
R
Borch-Johnsen
K
K
Pedersen
O
O
Enerbäck
S
S
Hansen
T
T
D001483:Base Sequence; D001824:Body Constitution; D002096:C-Peptide / Q000097:blood*; D017931:DNA Primers; D004268:DNA-Binding Proteins / Q000235:genetics*; D003718:Denmark; D003920:Diabetes Mellitus / Q000235:genetics*; D005260:Female; D051858:Forkhead Transcription Factors; D014644:Genetic Variation / Q000235:genetics*; D005951:Glucose Tolerance Test; D006801:Humans; D008297:Male; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D012016:Reference Values; D017384:Sequence Deletion; D014157:Transcription Factors / Q000235:genetics*; D044465:White People / Q000235:genetics
D002096:C-Peptide; D017931:DNA Primers; D004268:DNA-Binding Proteins; D051858:Forkhead Transcription Factors; D014157:Transcription Factors; C082078:mesenchyme fork head 1 protein