title: CPVL/CHN2 genetic variant is associated with diabetic retinopathy in Chinese type 2 diabetic patients.
abstract: OBJECTIVE
  Diabetic nephropathy and retinopathy are two important microvascular diabetes complications with a high concordance rate in diabetic patients. A recent genome-wide association study in type 1 diabetic patients of European descent identified four loci to be associated with diabetic nephropathy. The aim of this study was to test the effects of single nucleotide polymorphisms (SNPs) from these four loci on diabetic nephropathy and retinopathy in Chinese type 2 diabetic patients.
  
  
  METHODS
  In stage 1, we recruited 1,276 type 2 diabetic patients, including 378 patients with diabetic nephropathy but no retinopathy, 374 patients with diabetic retinopathy but no nephropathy, 244 patients with both diabetic retinopathy and nephropathy, and 280 control subjects with diabetes for >10 years and no diabetic retinopathy or nephropathy. Fifty-five SNPs from four loci (CPVL/CHN2, FRMD3, CARS, and IRS2) were genotyped. The SNPs that showed associations to diabetic retinopathy or nephropathy were genotyped in stage 2 samples for replication.
  
  
  RESULTS
  SNPs from CPVL/CHN2 and FRMD3 were associated with diabetic retinopathy with rs39059 and rs10868025 as the top SNPs (odds ratio [OR] 1.292, 95% CI 1.097-1.523, P = 0.0022, for rs39059; 1.201, 1.014-1.422, P = 0.0343, for rs10868025) in stage 1 samples. In stage 2 analysis, only rs39059 showed similar effect to diabetic retinopathy (OR 1.269, 0.989-1.628, P = 0.0689), and meta-analysis showed a significant association between rs39059 and diabetic retinopathy, with an OR of 1.285 (1.120-1.474, P = 0.0003). CPVL/CHN2 rs39059 was also associated with levels of diabetic retinopathy (P = 0.0007 for trend). However, no association was detected between these SNPs and diabetic nephropathy.
  
  
  CONCLUSIONS
  In this study, we found CPVL/CHN2 rs39059 was associated with diabetic retinopathy in the Chinese type 2 diabetic patients.
authors.affiliation: Shanghai Diabetes Institute, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai, China.
authors.forename: Cheng
authors.initials: C
authors.lastname: Hu
authors.forename: Rong
authors.initials: R
authors.lastname: Zhang
authors.forename: Weihui
authors.initials: W
authors.lastname: Yu
authors.forename: Jie
authors.initials: J
authors.lastname: Wang
authors.forename: Congrong
authors.initials: C
authors.lastname: Wang
authors.forename: Can
authors.initials: C
authors.lastname: Pang
authors.forename: Xiaojing
authors.initials: X
authors.lastname: Ma
authors.forename: Yuqian
authors.initials: Y
authors.lastname: Bao
authors.forename: Kunsan
authors.initials: K
authors.lastname: Xiang
authors.forename: Weiping
authors.initials: W
authors.lastname: Jia
mesh_terms: D000368:Aged; D000604:Amino Acyl-tRNA Synthetases / Q000235:genetics; D002268:Carboxypeptidases / Q000235:genetics*; D016022:Case-Control Studies; D002681:China; D003924:Diabetes Mellitus, Type 2 / Q000150:complications* / Q000235:genetics; D003930:Diabetic Retinopathy / Q000235:genetics* / Q000503:physiopathology; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D006801:Humans; D055504:Insulin Receptor Substrate Proteins / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D012720:Severity of Illness Index; D025521:Tumor Suppressor Proteins / Q000235:genetics
chemical_list: C562024:FRMD3 protein, human; C526297:IRS2 protein, human; D055504:Insulin Receptor Substrate Proteins; D009363:Neoplasm Proteins; D025521:Tumor Suppressor Proteins; C079844:beta-chimaerin; D002268:Carboxypeptidases; C508747:CPVL protein, human; D000604:Amino Acyl-tRNA Synthetases; C019975:cysteinyl-tRNA synthetase