RGD Reference Report - FOXC2 mRNA Expression and a 5' untranslated region polymorphism of the gene are associated with insulin resistance. - Rat Genome Database

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FOXC2 mRNA Expression and a 5' untranslated region polymorphism of the gene are associated with insulin resistance.

Authors: Ridderstrale, M  Carlsson, E  Klannemark, M  Cederberg, A  Kosters, C  Tornqvist, H  Storgaard, H  Vaag, A  Enerback, S  Groop, L 
Citation: Ridderstrale M, etal., Diabetes. 2002 Dec;51(12):3554-60.
RGD ID: 1601219
Pubmed: PMID:12453913   (View Abstract at PubMed)

The human transcription factor FOXC2 has recently been shown to protect against diet-induced insulin resistance in transgenic mice. We investigated the expression of FOXC2 in fat and muscle and performed a genetic analysis in human subjects. FOXC2 mRNA levels were increased in visceral compared with subcutaneous fat from obese subjects (12 +/- 4-fold; P = 0.0001), and there was a correlation between whole-body insulin sensitivity and FOXC2 mRNA levels in visceral fat (fS-insulin R = -0.64, P = 0.01, and homeostasis model assessment of insulin resistance [HOMA-IR] R = -0.68, P = 0.007) and skeletal muscle (fS-insulin R = -0.57, P = 0.03, and HOMA-IR R = -0.55, P = 0.04). Mutation screening of the FOXC2 gene identified a common polymorphism in the 5' untranslated region (C-512T). The T allele was associated with enhanced insulin sensitivity (HOMA-IR P = 0.007) and lower plasma triglyceride levels in females (P = 0.007). Also, the higher expression of FOXC2 in visceral than in subcutaneous fat was restricted to subjects homozygous for the T allele (P = 0.03 vs. P = 0.7). Our data suggest that increased FOXC2 expression may protect against insulin resistance in human subjects and that genetic variability in the gene may influence features associated with the metabolic syndrome.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
FOXC2HumanInsulin Resistance  IAGP DNA:polymorphism:5'ut:-512C>TRGD 
Foxc2RatInsulin Resistance  ISOFOXC2 (Homo sapiens)DNA:polymorphism:5'ut:-512C>TRGD 

Objects Annotated

Genes (Rattus norvegicus)
Foxc2  (forkhead box C2)

Genes (Homo sapiens)
FOXC2  (forkhead box C2)


Additional Information