Fetuin-A gene polymorphism and its serum level association with atherosclerotic vascular disease in type 2 diabetes patients with early diabetic kidney disease

Abstract

Background: The incidence of type 2 diabetes mellitus (T2DM) is increasing over the past years. Early identification and management of its complications, especially diabetic kidney disease (DKD), is of great importance. Multiple factors play a role in the pathogenesis of T2DM and DKD. We aimed to study Fetuin-A gene polymorphisms and Fetuin-A serum levels in T2DM patients with early DKD.

Methods: The present work was conducted on 120 patients with T2DM (60 patients with microalbuminuria and 60 without albuminuria), and 30 healthy subjects (as a control group). Serum Fetuin-A levels were measured with ELISA. Fetuin-A, Thr256Ser and Thr248Met polymorphisms were determined by PCR-RFLP.

Results: Patients with T2DM had a significantly higher mean serum Fetuin-A compared to controls (p < 0.001), while no difference was observed when comparing mean serum Fetuin-A in patients with microalbuminuria and patients without albuminuria (p = 0.916). Multivariate regression analysis demonstrated that carotid intima-media thickness (CIMT) and insulin resistance had positive correlations with serum Fetuin-A (p < 0.001 and p < 0.001, respectively). Ankle-brachial pressure index (ABPI) had a negative correlation with serum Fetuin-A (p=0.046), while Fetuin-A levels neither affected eGFR nor albuminuria. The distribution of the alleles of both polymorphisms showed increased frequency of TT (rs248) and GG (rs256) in patients without albuminuria compared to patients with microalbuminuria.

Conclusion: Increased serum Fetuin-A is associated with insulin resistance and increased risk of atherosclerosis in patients with T2DM, but is not associated with the development of DKD. TT (rs248) and GG (rs256) polymorphisms may be associated with lower risk of DKD.