Chemokine Receptor Genotype Is Associated With Diabetic Nephropathy in Japanese With Type 2 Diabetes
- Kunihiro Nakajima1,
- Yasushi Tanaka1,
- Takashi Nomiyama1,
- Takeshi Ogihara1,
- Lianshan Piao2,
- Ken Sakai1,
- Tomio Onuma1 and
- Ryuzo Kawamori1
- 1Department of Medicine, Metabolism and Endocrinology, Juntendo University School of Medicine, Tokyo, Japan
- 2Department of Medicine and Endocrinology, Yanbian University Hospital, Yanji, China
Abstract
Glomerular infiltration of monocytes/macrophages occurs in diabetic patients with nephropathy, and chemokine receptor signals are thought to play a key role in the development of nephropathy. Recently, polymorphism of the chemokine receptor (CCR)2 coding region V64I and the CCR5 promoter region 59029 (G/A) have been identified. Accordingly, we evaluated the effects of these genotypes on diabetic nephropathy. CCR2 V64I and CCR5 59029 (G/A) were detected by polymerase chain reaction–restriction fragment–length polymorphism in 401 patients with type 2 diabetes who had a serum creatinine <2.0 mg/dl. Although the CCR2 V64I genotype showed no association with nephropathy, the frequency of the CCR5 59029 A-positive genotype (G/A or A/A) was significantly higher in patients with microalbuminuria (urinary albumin-to-creatinine ratio [ACR] ≥30 and <300 mg/gCre, 86%) and patients with macroalbuminuria (ACR ≥300 mg/gCre, 87%) than in patients with normoalbuminuria (ACR <30 mg/gCre, 75%; P = 0.0095). Polytomic logistic regression analysis showed that the CCR5 59029 A-positive genotype was associated with nephropathy (odds ratio 2.243, P = 0.0074). These results suggest that the CCR5 promoter 59029 A genotype may be an independent risk factor for diabetic nephropathy in patients with type 2 diabetes.
Footnotes
-
Address correspondence and reprint requests to Yasushi Tanaka, MD, Department of Medicine, Metabolism and Endocrinology, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan. E-mail: y-tanaka{at}med.juntendo.ac.jp.
Received for publication 9 May 2001 and accepted in revised form 12 October 2001.
ACR, albumin-to-creatinine ratio; CCR, chemokine receptor; CVD, cardiovascular disease; IL-1β, interleukin-1β; IMT, intima-media thickness; MCP-1, monocyte chemoattractant protein 1; PCR, polymerase chain reaction; RANTES, regulated upon activation, normal T-cell expressed and secreted; RFLP, restriction fragment–length polymorphism; SNP, single-nucleotide polymorphism; TNF-α, tumor necrosis factor-α.
