Chemokine receptor genotype is associated with diabetic nephropathy in Japanese with type 2 diabetes.
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] > or = 30 and <300 mg/gCre, 86%) and patients with macroalbuminuria (ACR > or = 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.
Nakajima
Kunihiro
K
Department of Medicine, Metabolism and Endocrinology, Juntendo University School of Medicine, Tokyo, Japan.
Tanaka
Yasushi
Y
Nomiyama
Takashi
T
Ogihara
Takeshi
T
Piao
Lianshan
L
Sakai
Ken
K
Onuma
Tomio
T
Kawamori
Ryuzo
R
D000419:Albuminuria / Q000235:genetics / Q000503:physiopathology; D044466:Asian People / Q000235:genetics; D002784:Cholesterol / Q000097:blood; D008076:Cholesterol, HDL / Q000097:blood; D003404:Creatinine / Q000097:blood; D004251:DNA Transposable Elements; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics*; D003928:Diabetic Nephropathies / Q000235:genetics*; D005260:Female; D005838:Genotype; D006442:Glycated Hemoglobin / Q000032:analysis; D006801:Humans; D007564:Japan; D008297:Male; D008875:Middle Aged; D007703:Peptidyl-Dipeptidase A / Q000235:genetics; D054390:Receptors, CCR2; D019713:Receptors, CCR5 / Q000235:genetics; D019707:Receptors, Chemokine / Q000235:genetics*; D017384:Sequence Deletion; D012907:Smoking
D002784:Cholesterol; D008076:Cholesterol, HDL; D003404:Creatinine; D004251:DNA Transposable Elements; D006442:Glycated Hemoglobin; D007703:Peptidyl-Dipeptidase A; D054390:Receptors, CCR2; D019713:Receptors, CCR5; D019707:Receptors, Chemokine; C515334:CCR2 protein, human