Chemokine receptor genotype is associated with diabetic nephropathy in Japanese with type 2 diabetes.
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] > 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.
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ABSTRACT: To test whether the genetic variant CCR5Delta32 in the CC-chemokine receptor 5, which is known to lead to CCR5 deficiency, is associated with mortality in type 2 diabetes patients. We examined the effect of presence or absence of the CCR5Delta32 on overall and cardiovascular mortality risk in the Zwolle Outpatient Diabetes project Integrating Available Care (ZODIAC) cohort, a type 2 diabetes patient cohort. We studied 756 patients with a mean duration of follow-up of 5.4 (+/- 1.4) years. 194 patients died during follow up of which 83 were cardiovascular deaths. 144 subjects (19%) carried the CCR5Delta32 deletion. CCR5Delta32 carriers had an adjusted hazard ratio of 0.62 (95%CI: 0.40-0.96; p=0.03) for all-cause mortality and 0.63 (95%CI: 0.33-1.19; p=0.16) for cardiovascular mortality. The presence of CCR5Delta32 is associated with better survival in type 2 diabetes patients. These data suggest that it is worthwhile to explore the protective potential of pharmacological blockade of CCR5 in type 2 diabetic patients.Diabetes research and clinical practice 10/2009; 86(2):140-5. DOI:10.1016/j.diabres.2009.08.013 · 2.54 Impact Factor
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ABSTRACT: The importance of showing up at the right place at the right time is instilled in leukocytes, just as it is in each one of us, by our parents. The fact that leukocyte infiltration of a newly established allograft typically presages the development of acute rejection is the downside of having an exquisitely tuned and finely balanced immune system. Chemokines binding to their receptors on leukocytes mediate the behind-the-scenes plays between antigen-presenting cells and host T cells in lymphoid tissues, the actual here-and-now, in-your-face fulmi- nant immune responses that can acutely destroy a graft, and also, as seems increasingly apparent, smoldering inflammatory responses seen clinically as chronic rejection. Given these complex and multifaceted roles, knowledge of chemokine bi- ology is no longer just for the aficionado. Indeed, genetically based differences in chemokine-dependent responses may be yet another thing for which to blame (or thank) our parents, as evidenced by clinical studies of the effects of chemokine and chemokine receptor polymorphisms on allograft rejection and allograft survival (1-3).Journal of the American Society of Nephrology 04/2002; 13(3):821-4. · 9.47 Impact Factor
- Nephrology Dialysis Transplantation 04/2003; 18(3):457-9. DOI:10.1093/ndt/18.3.457 · 3.49 Impact Factor