Role of the FOXC2 -512C>T polymorphism in type 2 diabetes: possible association with the dysmetabolic syndrome.
OBJECTIVE
Overexpression of the human transcription factor FOXC2 gene (FOXC2) protects against insulin resistance in mice and a common FOXC2 polymorphism (-512C>T) has been suggested to be associated with insulin resistance in humans. Here, we addressed the potential role for FOXC2 as a candidate gene for type 2 diabetes and associated phenotypes.


METHODS
A case-control study was performed in 390 type 2 diabetic patients and 307 control subjects. The number of patients was increased to a total of 768 subjects for further study of phenotypic differences relating to the dysmetabolic syndrome relative to genetic variation. The FOXC2 -512C>T polymorphism was genotyped by a restriction fragment length polymorphism PCR assay.


RESULTS
FOXC2 -512C>T allele and genotype distribution did not differ between patients with type 2 diabetes and control subjects, but the C/C genotype was associated with increased body mass index (BMI, kg/m2) (Pa=0.03) among type 2 diabetic patients. The FOXC2 -512C>T polymorphism was a significant independent predictor of BMI (P=0.001) in a multiple regression model including age, gender and affection status. We found no significant association with type 2 diabetes-related metabolic parameters but that the C-allele (P=0.01) and C/C and C/T genotypes (P=0.03) were significantly over-represented in type 2 diabetic males with a concomitant diagnosis of dysmetabolic syndrome.


CONCLUSIONS
We conclude that FOXC2 is associated with obesity and metabolic deterioration but does not contribute to an increased risk for type 2 diabetes.
Carlsson
E
E
Department of Endocrinology, Lund University, University Hospital MAS, Malmö, Sweden. emma.carlsson@endo.mas.lu.se
Groop
L
L
Ridderstråle
M
M
D000368:Aged; D015992:Body Mass Index; D016022:Case-Control Studies; D004268:DNA-Binding Proteins / Q000235:genetics*; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics*; D005260:Female; D051858:Forkhead Transcription Factors; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D007333:Insulin Resistance / Q000235:genetics; D008297:Male; D024821:Metabolic Syndrome / Q000235:genetics*; D008875:Middle Aged; D009765:Obesity / Q000235:genetics; D010641:Phenotype; D011110:Polymorphism, Genetic; D014157:Transcription Factors / Q000235:genetics*
D004268:DNA-Binding Proteins; D051858:Forkhead Transcription Factors; D014157:Transcription Factors; C082078:mesenchyme fork head 1 protein