title: Variations in CCR5, but not HFE, ELMO1, or SLC12A3, are associated with susceptibility to kidney disease in north Indian individuals with type 2 diabetes.
abstract: BACKGROUND
  Diabetic nephropathy (DN), the leading cause of end-stage renal disease worldwide, may have a genetic component. In the present study, we investigated variations in a set of genes with susceptibility to DN in a north Indian population.
  
  
  METHODS
  Four genes (HFE, ELMO1, SLC12A3, and CCR5) were selected on the basis of reported association with type 2 diabetes and nephropathy. In all, 417 diabetic subjects (215 without kidney disease [DM] and 202 with DN) and 197 healthy controls (HC) were evaluated for variations in HFE (845 G>A and 187G>C), SLC12A3 (g.34372G>A), CCR5 (59029A>G), and ELMO1 (+9170 G>A). Polymorphism analysis was performed by polymerase chain reaction-restriction fragment length polymorphism and Taqman allele discrimination assays.
  
  
  RESULTS
  Significant differences were found in genotype and allelic frequency in SLC12A3 (g.34372G>A) between diabetic subjects and HC (P < 0.03). There were no differences in the SLC12A3 g.34372G>A (AA+GA) genotype between diabetic subjects with and without nephropathy. However, the CCR5 59029AA genotype and A allele were significantly more frequent in diabetics compared with the HC (P = 0.01 and 0.03, respectively) and subjects with DN versus DM (P = 0.002 and 0.01, respectively). For ELMO1 (+9170 G>A), the GG genotype frequency was higher in the diabetic versus HC group. There were no differences in the frequency of HFE-845 G>A and HFE-187G>C among the groups.
  
  
  CONCLUSIONS
  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 the SLC12A3 34372 AA genotype is associated with a reduced risk of diabetes.
authors.affiliation: Department of Nephrology, Postgraduate Institute of Medical Education and Research, Chandigarh, India.
authors.forename: Ashok K
authors.initials: AK
authors.lastname: Yadav
authors.forename: Vinod
authors.initials: V
authors.lastname: Kumar
authors.forename: Pinaki
authors.initials: P
authors.lastname: Dutta
authors.forename: Anil
authors.initials: A
authors.lastname: Bhansali
authors.forename: Vivekanand
authors.initials: V
authors.lastname: Jha
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics*; D000328:Adult; D000368:Aged; D000483:Alleles; D016022:Case-Control Studies; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000235:genetics*; D003928:Diabetic Nephropathies / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D000071020:Hemochromatosis Protein; D015395:Histocompatibility Antigens Class I / Q000235:genetics*; D006801:Humans; D007194:India; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D019713:Receptors, CCR5 / Q000235:genetics*; D064486:Solute Carrier Family 12, Member 3 / Q000235:genetics; D044465:White People
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C584933:CCR5 protein, human; C465214:ELMO1 protein, human; C103673:HFE protein, human; D000071020:Hemochromatosis Protein; D015395:Histocompatibility Antigens Class I; D008565:Membrane Proteins; D019713:Receptors, CCR5; C578874:SLC12A3 protein, human; D064486:Solute Carrier Family 12, Member 3
keywords: ELMO1; HFE; SLC12A3; diabetic nephropathy; genetics; type 2 diabetes; 关键词：糖尿病肾病，ELMO1，遗传学，HFE，SLC12A3，2型糖尿病