Is CCR5-Delta32 mutation associated with diabetic nephropathy in type 2 diabetes?

To the Editor: Immunological factors like the chemokine-receptor axis recently were proved to have crucial roles in diabetes and its complications.1 CCR5 is a G-protein CC (CCL3, CCL4, CCL5) chemokine receptor, which recruits immune cells to the site of infection, inflammation and injuries, including nephropathic disease.2 Previous studies demonstrated that a mutation in the unique exon (exon 1) of the CCR5 and deletion of 32 nucleotides (also known as Δ32) leads to decreased expression and function of CCR5.2 Due to its immunomodulatory functions, the CCR5-Δ32 mutation seems to play a key role in autoimmune and inflammatory diseases.3 This study aimed to analyze the CCR5-Δ32 mutation in type 2 diabetic patients with and without diabetic nephropathy (DN). Samples were collected from 100 type 2 diabetic patients with DN, 200 type 2 diabetic patients without DN and 300 healthy controls. The groups were of the same sex, roughly the same age, diabetes history and socioeconomic status. DNA extraction and Gap-PCR reactions were performed as our previous study.4 Our findings indicated the absence of CCR5-Δ32 in type 2 diabetic patients with and without DN, while only two controls showed a heterozygotic pattern of mutation. A significant difference was not observed in the CCR5-Δ32 mutation in diabetic patients and controls (P <.78).

The CCR5 affects the immune cell function,1 and thus, the CCR5-Δ32 mutation leads to decreased CCR5 expression and influences the function of these cells.3 In agreement with our results, Kalev and colleagues reported a lack of association between CCR5-Δ32 mutation and DN in native Estonian type 2 diabetic patients.2 Studies also demonstrated that type 1 diabetes is not related to CCR5-Δ32.56 Like other investigators, we could not find any association between development of DN and CCR5-Δ32 mutation. Based on our findings and others, it seems that CCR5-Δ32 in diabetic type 2 patients is independent of geographical and ethnic factors. Prasad et al, showed that CCR5-Δ32 is not related to nephropatic type 2 diabetes in Asian-Indians.7 Another study in type 1 diabetic patients with renal failure showed that male carriers with CCR5-Δ32 mutation had a higher risk of nephropathy.8 To our knowledge none of research groups showed an association of CCR5-Δ32 with nephropathy in type 2 diabetic patients, but other CCR5 gene polymorphisms are associated with these nephropathies.79 Overall, based on the results of this study and globally collected data, it is likely that the CCR5-Δ32 mutation is not associated with diabetes and the nephropathic complications of diabetes.