Association of chemokine ligand 5/chemokine receptor 5 gene promoter polymorphisms with diabetic microvascular complications: A meta‐analysis. Issue 2 (21st August 2015) - Zhang, Zhongwen
Abstract: Aims/Introduction: Chemokine ligand 5 (CCL5) is a member of the CC‐chemokine family expressed in various organs. It contributes to the migration of monocytes/macrophages into injured vascular walls by binding with its receptor chemokine receptor 5 (CCR5). Many studies have accessed the association between CCL5/CCR5 gene promoter polymorphisms and diabetic microvascular complications (DMI). However, the results are conflicting and inconclusive. The aim of the present study was to evaluate the association more precisely. Materials and Methods: Trials were retrieved through PubMed, Embase, Medline, China National Knowledge Infrastructure, Web of Science and Cochrane database without restrictions on language. The pooled odds ratio (OR) and 95% confidence interval (CI) were used to describe the strength of association with DMI. Results: Data were obtained from 11 case–control studies that included 2, 737 DMI patients and 2, 435 diabetic control subjects. In the overall analysis, the CCL5‐403 G/A and CCL5‐28 C/G gene polymorphisms were not significantly associated with the risk of DMI. However, CCR5‐59029 G/A was an independent risk factor of DMI in a dominant model (OR 1.77, 95% CI 1.06–2.97). Subgroup analysis showed that the risk of the CCR5 59029A‐positive genotype was significant in Asians (OR 2.08, 95% CI 1.68–2.57). In addition, the CCR5 59029A‐positive genotype was associated with increased risk of albuminuria. Conclusions: There were no associations of CCL5 gene promoter polymorphism with the risk of DMI. However, the 59029A polymorphism in CCR5 might affect individual susceptibility for DMI. Abstract : In this study, we found that CCL5 (CCL5‐403 G/A and CCL5‐28 C/G) gene promoter polymorphisms are not significantly associated with the risk of diabetic microvascular complications, however, CCR5 (CCR5‐59029 G/A) gene promoter polymorphism is an independent risk factor of diabetic microvascular complications. In addition, CCR5 59029A‐positive genotype was associated with increased risk of albuminuria. Our findings suggest that CCR5 might present as a novel target for early preventive care of diabetic microvascular complications.