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.
- [Show abstract] [Hide abstract]
ABSTRACT: BACKGROUND: Autoimmune mechanisms play a role in the pathophysiology of chronic urticaria. As the genetic background of autoimmunity is well proven, the role of genetics in chronic urticaria is hypothesised. METHODS: 153 unrelated chronic spontaneous urticaria patients with a positive result of autologous serum skin test were included into the study, as were 115 healthy volunteers as control group. In all subjects we analysed CCR2 G190A and CCR5 d32 polymorphisms. RESULTS: We noticed higher prevalence of CCR2 A allele as well as lower frequency of CCR5 d32 in chronic urticaria group in comparison to control group, with borderline statistical significance. Additionally, we assumed haplotype Gd statistically significant negative chronic urticaria association with tendency to higher frequency of Aw haplotype in this group. CONCLUSIONS: The results of our study imply the role of autoimmune components in chronic urticaria pathogenesis and present chronic urticaria as possibly genetically related disorder.Allergologia et Immunopathologia 05/2013; · 1.23 Impact Factor
- International Congress Series 01/2003; 1253:149-161.
- [Show abstract] [Hide abstract]
ABSTRACT: Diabetic nephropathy (DN), the leading cause of end-stage renal disease worldwide, might have a genetic component. We investigated variations in a set of genes with susceptibility to DN in north Indian population. We selected four genes (HFE, ELMO1, SLC12A3 and CCR5), based on reported association with type 2 diabetes and nephropathy. A total of 417 diabetic subjects: 215 without kidney disease (DM), 202 with DN and 197 healthy controls (HC) were evaluated for variation in HFE (845 G>A and 187G>C) SLC12A3 (g.34372G>A), CCR5 (59029A>G) and ELMO1 (+9170 G>A) genes. Polymorphism analysis was performed by PCR-RFLP and Taqman allele discrimination assay. A significant difference was found in genotype and allelic frequency in SLC12A3 (g.34372G>A) between diabetic and HC (p<0.03). No difference in SLC12A3 g.34372G>A (AA+GA) genotype was noted between diabetics with and without nephropathy. CCR5 59029AA genotype and A allele were significantly more frequent in diabetics as compared to HC (p=0.01, 0.03) and in DN as compared to DM (p=0.002,0.01). In ELMO1 (+9170 G>A), GG genotype frequency was higher in diabetic group as compared to HC. There was no difference in HFE-845 G>A and HFE-187G>C frequency between the groups. This study shows that the CCR5 AA genotype is over-represented in subjects with kidney disease due to type 2 diabetes. The CCR5 59029G>A and ELMO1 (+9170 G>A) loci are more frequent, and SLC12A3 34372 AA genotype is associated with reduced risk of diabetes.Journal of Diabetes 01/2014; · 2.94 Impact Factor