The Fatty Acid–Binding Protein-2 A54T Polymorphism Is Associated With Renal Disease in Patients With Type 2 Diabetes

Abstract

The intestinal fatty-acid binding protein-2 (FABP2) gene codes a protein responsible for the absorption of longchain fatty acids. To test whether FABP2 is a candidate gene for renal disease in patients with type 2 diabetes, a functional A54T polymorphism was genotyped in 1,042 Brazilians with type 2 diabetes. Patients were classified as having normoalbuminuria (urinary albumin excretion [UAE] <20 g/min; n ‫؍‬ 529), microalbuminuria (UAE 20 -199 g/min; n ‫؍‬ 217), or proteinuria (UAE >199 g/ min; n ‫؍‬ 160). Patients with end-stage renal disease (ESRD) (n ‫؍‬ 136) were also included. D iabetic nephropathy develops in up to 40% of diabetic patients at most, even when high glucose levels are maintained for long periods of time (1). Epidemiological (2) and familial (3-5) studies have demonstrated that genetic susceptibility contributes to the development of diabetic nephropathy in both type 1 and type 2 diabetes. The precise genetic model underlying diabetic nephropathy susceptibility is uncertain, but several genes with a minor effect have been associated with diabetic nephropathy (6). Insulin resistance has been implicated in the development of diabetic nephropathy (7), and aggregation of components of the metabolic syndrome is associated with a high prevalence of diabetic nephropathy (8). The intestinal fatty acidbinding protein-2 (FABP2) gene codes a protein expressed in enterocytes and is responsible for the absorption of long-chain fatty acids (9). A single nucleotide polymorphism (SNP) in the FABP2 gene at codon 54 causes an amino acid change (Ala 3 Thr). This change affects the ability of the protein to bind and transport dietary fatty acids (9). Serum saturated fatty acids might induce endothelial dysfunction (10) and are related to increased cardiovascular mortality (11). We have previously reported increased levels of serum saturated fatty acids in patients with type 2 diabetes and microalbuminuria (12), as well as a reduction in albumin excretion rate after replacement of red meat (high content of saturated fatty acids) with chicken (low content of saturated fatty acids) in these patients (13). Based on these observations, we hypothesized that genetically predisposed subjects exposed to a diet with a high content of saturated fatty acids might be at high risk for developing renal disease. Therefore, we decided to examine whether FABP2 is a susceptibility gene for renal disease in patients with type 2 diabetes. Our study focused particularly on the A54T polymorphism, since this polymorphism results in a functionally altered FABP2 protein. Additional information for this article can be found in an online appendix at http://diabetes.diabetesjournals.org. RESEARCH DESIGN AND METHODSESRD, end-stage renal disease; FABP2, fatty acid-binding protein-2; IHD, ischemic heart disease; SNP, single nucleotide polymorphism; UAE, urinary albumin excretion.

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