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

Nilsson, Emma A LU ; Groop, Leif LU and Ridderstråle, Martin LU (2005) In International Journal of Obesity 29(Dec 14). p.268-274
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... (More)
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. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
case-control association study, dysmetabolic syndrome, type 2 diabetes, noninsulin-dependent diabetes, forkhead transcription factor
in
International Journal of Obesity
volume
29
issue
Dec 14
pages
268 - 274
publisher
Nature Publishing Group
external identifiers
  • wos:000226981400003
  • pmid:15597109
  • scopus:14744289046
ISSN
1476-5497
DOI
10.1038/sj.ijo.0802876
language
English
LU publication?
yes
id
73214424-f94a-4b9a-a023-29047b5a7a56 (old id 132039)
date added to LUP
2007-07-17 09:47:01
date last changed
2017-11-05 03:48:45
@article{73214424-f94a-4b9a-a023-29047b5a7a56,
  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.},
  author       = {Nilsson, Emma A and Groop, Leif and Ridderstråle, Martin},
  issn         = {1476-5497},
  keyword      = {case-control association study,dysmetabolic syndrome,type 2 diabetes,noninsulin-dependent diabetes,forkhead transcription factor},
  language     = {eng},
  number       = {Dec 14},
  pages        = {268--274},
  publisher    = {Nature Publishing Group},
  series       = {International Journal of Obesity},
  title        = {Role of the FOXC2 -512C>T polymorphism in type 2 diabetes: possible association with the dysmetabolic syndrome.},
  url          = {http://dx.doi.org/10.1038/sj.ijo.0802876},
  volume       = {29},
  year         = {2005},
}