Dataset Information

Association of chemokine ligand 5/chemokine receptor 5 gene promoter polymorphisms with diabetic microvascular complications: A meta-analysis.

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.

SUBMITTER: Zhang Z

PROVIDER: S-EPMC4773673 | biostudies-literature | 2016 Mar

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Association of chemokine ligand 5/chemokine receptor 5 gene promoter polymorphisms with diabetic microvascular complications: A meta-analysis.

Zhang Zhongwen Z Zhang Xiaoqian X Dong Jianjun J Gao Weiyi W Liu Fupeng F Zhao Junyu J Wu Xiaoyun X Guan Xiaoling X Liu Ju J Liao Lin L

Journal of diabetes investigation 20150821 2

<h4>Aims/introduction</h4>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 ...[more]

PMID: 27042273

Similar Datasets

Project description:AimsAlanine aminotransferase (ALT) is positively related to diabetes risk in observational studies, whereas Mendelian randomization supports a linear causal association. In contrast, the relationship between ALT and diabetic nephropathy, and diabetic retinopathy is counter-intuitive in observational studies. Furthermore, no MR study has examined their causal association. The study aimed to investigate whether genetically determined ALT has a causal effect on diabetic nephropathy and diabetic retinopathy.MethodsGenetic instruments associated with ALT (P < 5×10-8) were obtained from a recent genome-wide association study (GWAS) that included 437,267 individuals of European ancestry. Summary data of diabetic microvascular complications were derived from the FinnGen study (3,283 cases and 181,704 controls for diabetic nephropathy, and 14,584 cases and 176,010 controls for diabetic retinopathy, both were of European ancestry). Effect estimation and pleiotropy testing were performed using inverse variance weighted (IVW), MR-Egger regression, weighted median, and mode-based estimator methods. We additionally performed sensitivity analysis excluding proxy single nucleotide polymorphisms (SNPs) or lowering the GWAS significance threshold (P < 5×10-7) to test the robustness of the results.ResultsBased on IVW, a 2-fold increase in genetically determined ALT level was positively associated with diabetic nephropathy (odd ratio, [95% confidence interval], 1.73 [1.26-2.37], P = 0.001) and diabetic retinopathy (1.29 [1.08-1.54], P = 0.005), but a null causal association in three pleiotropy robust methods, namely, MR-Egger, weighted median and mode-based estimator. We obtained similar results in the sensitivity analysis of excluding proxy SNPs or lowering the GWAS significance threshold.ConclusionsWith caution, we concluded that ALT plays no linear causal role in developing both diabetic nephropathy and diabetic retinopathy. Further investigations are required to test the hypothesis of a non-linear causal association.

Project description:We studied JAZF1, ABCC8, KCNJ11and Notch2 gene expression and vitamin D receptor (VDR) polymorphisms (Fok1 and Bsm1) in patients with type 2 diabetes mellitus (T2DM) and tried to find out their association with microvascular complications in these patients.The study was conducted on 180 patients (93 complicated and 87 noncomplicated) and 150 healthy subjects. Reverse-transcriptase polymerase chain reaction (RT-PCR) was used to assess gene expression and real-time PCR was used to detect VDR genotypes. Serum vitamin D was assessed using Elisa technique.After adjustment for age, sex, body mass index and glycated hemoglobin, altered Notch2 gene expression was found between patients and controls and between complicated and noncomplicated cases (p = 0.001 and 0.001, respectively) and ABCC8 gene expression showed significant difference between patients and controls only (p = 0.003), while JAZF1and KCNJ11 expression showed no significant difference between the studied groups (p = 0.3 and 0.4, respectively). Serum vitamin D level was decreased in patients compared with controls (p = 0.001), while no difference was detected between complicated and noncomplicated cases (p = 0.1). Our results revealed no significant difference in VDR Fok1 and Bsm1 genotype distributions (p = 0.7 and 0.1, respectively) and allele frequencies (p = 0.4 and 0.1, respectively) between patients and controls. Patients with complications showed increased frequencies of Fok1GG genotype and G allele, while patients without complications showed increased frequencies of AA, then AG Fok1 genotype and A allele (p = 0.001 and 0.001, respectively). In addition, the frequencies of CC Bsm1 genotype and C allele were significantly higher among patients with complications, while frequencies of TT Bsm1 genotype and T allele were significantly higher among patients without complications (p = 0.02 and 0.003, respectively).Altered expression of Notch2 and ABCC8 genes may play a role in the pathogenesis of T2DM. Altered expression of Notch2 and VDR polymorphisms may play a role in the development of microvascular complications in diabetic patients. These results may assist in early identification and management of diabetic complications.

Dataset Information

Association of chemokine ligand 5/chemokine receptor 5 gene promoter polymorphisms with diabetic microvascular complications: A meta-analysis.

Publications

Association of chemokine ligand 5/chemokine receptor 5 gene promoter polymorphisms with diabetic microvascular complications: A meta-analysis.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets