Role of the FOXC2–512C> T polymorphism in type 2 diabetes: possible association with the dysmetabolic syndrome

E Carlsson, L Groop, M Ridderstråle - International journal of obesity, 2005 - nature.com
International journal of obesity, 2005nature.com
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. MATERIALS AND METHODS: A case–control study was performed
in 390 type 2 diabetic patients and 307 control subjects. The number of patients was …
Abstract
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.
MATERIALS AND 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/m 2)(P a= 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.
CONCLUSION:
We conclude that FOXC2 is associated with obesity and metabolic deterioration but does not contribute to an increased risk for type 2 diabetes.
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