ABSTRACT
The development and progression of diabetic microvascular complications including nephropathy are related to the degree of glycemic control and oxidative stress and may be influenced by genetic factors. The aim of the present study has been to investigate the association between haptoglobin [Hp] gene polymorphism and the occurrence of diabetic nephropathy in patients with type 2 diabetes mellitus and to find a possible link between haptoglobin phenotypes and inflammatory parameters; serum C - reactive protein [CRP], interleukin- 6 [IL - 6] and haptoglobin. The study included 60 normotensive type 2 diabetic patients of more than 5 years duration categorized in 3 equal groups according to urinary albumin excretion [UAE] into normo, micro and macroalbuminuric. In addition, 20 individuals of matched age and sex were selected to serve as a control group. Serum CRP, IL - 6 and haptoglobin concentrations were measured and haptoglobin phenotyping was conducted using polyacrylamide gel electrophoresis. The frequency of haptoglobin phenotype 1- 1 [Hp 1 - 1] in diabetic patients with normoalbuminuria was 7 of 20 [35%] as compared with diabetics with macroalbuminuria, 1 of 20 [5%] [p = 0.02] however, the frequency of Hp 2-2 was greater in diabetics with macroalbuminuria, 12 of 20 [60%] as compared with those with normoalbuminuria or controls, 5 of 20 [25%] [p= 0.03]. Patients with diabetic nephropathy [micro- or macroalbuminuria] had higher levels of serum CRP IL-6 and haptoglobin than those without nephropathy [normoalbuminuria]. Serum haptoglobin levels in type 2 diabetics were higher in Hp phenotype 2-2 as compared with Hp 1-1 however, serum CRP and IL - 6 levels did not differ significantly between haptoglobin phenotype groups. Moreover, there was significant positive correlations between urinary albumin excretion and serum levels of CRP, lL-6 and haptoglobin in diabetic patients. From this study, it could be concluded that haptoglobin phenotype 2-2 is considered as a major susceptibility gene for the development of nephropathy in type 2 diabetic patients. In addition, the significant association between inflammatory parameters and UAE indicates that inflammation may be a pathogenic mechanism of renal injury in type 2 diabetics. Moreover, serum interleukin - 6 and haptoglobin may be good prognostic factors for the development of nephropathy in the course of diabetes mellitus