Correlations of FOXC2 Gene Expression and Polymorphism with Type 2 Diabetes Mellitus

Background: To detect the protein and mRNA expression levels of forkhead box C2 (FOXC2) in visceral adipose tissues with type 2 diabetes mellitus (T2DM) as well as the polymorphism of serum FOXC2 gene, and to discuss the correlations of FOXC2 with T2DM and with relevant indices of adipose metabolism. Methods: A total of 18 T2DM patients and 18 non-diabetic patients receiving abdominal surgery in our hospital were randomly selected. The FOXC2 protein and mRNA expressions in greater-omental adipose tissues were detected by Western blotting and RT-PCR. The C-512T gene polymorphism in the FOXC2 gene 5' non-translated region was detected by PCR-RFLP. The correlations of FOXC2 gene polymorphism with FOXC2 protein and mRNA expressions in adipose tissues, and the correlations between FOXC2 gene and glycolipid metabolic indices were analyzed. Then the roles of the FOXC2 gene in glycolipid metabolism were discussed. Results: The FOXC2 protein and mRNA expression levels in the abdominal greater-omental adipose tissues are significantly lower in T2DM patients than in normal people (p < 0.01). The FOXC2 protein concentrations are significantly correlated with fasting plasma glucose (FPG) and triglyceride (TG) levels (p < 0.01). FOXC2 protein concentration is also correlated with the homeostasis model assessment-insulin resistance index (HOMA-IR) (p < 0.05). FOXC2 protein expression level is positively correlated with FOXC2 mRNA expression (p = 0.015). HOMA-IR is significantly correlated with FOXC2 gene mRNA expression (p = 0.002). The correlations between FOXC2 protein expression and T2DM are manifested by the ability to alleviate insulin resistance and improve the regulation of sugar metabolism by insulin. FOXC2 gene mRNA expression is negatively correlated with plasma FPG level (p < 0.01) and TG level (p < 0.05). FOXC2 gene C-512T polymorphism with protein and mRNA expressions and HOMA-IR: C-512T genotypes are not significantly different in the FOXC2 protein and mRNA expressions (p > 0.05). In all cases, the patients with T/T genotype have significantly smaller HOMA-IR than those with C/C and C/T (p = 0.03). The FOXC2 protein and mRNA expression levels are not correlated with the C-512T gene polymorphism. HOMA-IR is significantly correlated with C-512T gene polymorphism (p < 0.05). Conclusions: FOXC2 gene protein and mRNA expression levels are correlated with hyperglycaemia and high TG. The high FOXC2 expressions in visceral adipose tissues are manifested as reduction of blood glucose and blood lipid levels, thereby reducing insulin resistance. The FOXC2 protein and mRNA expression levels in visceral adipose tissues are significantly lower in T2DM patients than in non-diabetic patients, indicating that the FOXC2 protein expression is correlated with glycolipid metabolism. The FOXC2 gene C-512T polymorphism is not correlated with the FOXC2 protein or RNA expression in adipose tissues. HOMA-IR is significantly correlated with the C-512T gene polymorphism. These results indicate that FOXC2 gene is associated with the glycolipid metabolic abnormality in T2DM patients.