The association of chemokine receptor 5 gene 59029A/G polymorphisms with diabetic nephropathy in type 2 diabetic patients

Jeon, Hyun Jeong; Kim, Oak Hee; Oh, Tae Keun

Abstract

BACKGROUND/AIMS: Chemokine receptor 5 (CCR5) is a receptor for several chemokines, including regulated upon activation, normal T-cell-expressed and -secreted (RANTES; also known as CCL5) and macrophage inflammatory protein 1 (MIP-1), and mediates the recruitment of monocytes and their differentiation to macrophages during the inflammatory process. As such, CCR5 plays an important role in the development and progression of atherosclerosis, which has an underlying inflammation component and contributes to the development or progression of diabetic complications. Several studies have reported that a genetic variation of the CCR5 gene with A/G at basepair 59029 (59029 A/G) was associated with diabetic complications, although conflicting data exist. We evaluated the association of the CCR5 59029 A/G polymorphism with diabetic complications in type 2 diabetes patients.
METHODS
We conducted a case-control study, enrolling 325 patients with type 2 diabetes. We examined the association of CCR5 genotypic variations with diabetic nephropathy, retinopathy, and macrovascular complications such as coronary heart disease and stroke. Genotyping was performed using the polymerase chain reaction and restriction fragment length polymorphism technology with Bsp1286I restriction enzyme.
RESULTS
We determined no allelic association of CCR5 59029 A/G with diabetic nephropathy (p=0.500) in the male or female patients. Diabetic retinopathy and macrovascular complications such as coronary heart disease and stroke were not associated with the 59029 A/G polymorphism. Among those patients with diabetic nephropathies, those with the GG genotype showed a tendency toward higher serum levels of LDL-cholesterol.
CONCLUSIONS
These results suggest that that the 59029 A/G polymorphism of the CCR5 gene is not associated with diabetic complications in type 2 diabetes patients. Further studies are required to understand the role of CCR5 polymorphisms in the development of diabetic complications.