title: Common variants in or near ZNRF1, COLEC12, SCYL1BP1 and API5 are associated with diabetic retinopathy in Chinese patients with type 2 diabetes.
abstract: OBJECTIVE
  Three recent genome-wide association studies (GWAS) identified several single-nucleotide polymorphisms (SNPs) with modest effects on diabetic retinopathy in Mexican-American and white patients with diabetes. This study aimed to evaluate the effects of these variants on diabetic retinopathy in Chinese patients with type 2 diabetes.
  
  
  METHODS
  A total of 1,972 patients with type 2 diabetes were recruited to this study, including 819 patients with diabetic retinopathy and 1,153 patients with diabetes of ≥5 years duration but without retinopathy. Forty SNPs associated with diabetic retinopathy in three GWAS were genotyped. Fundus photography was performed to diagnose and classify diabetic retinopathy.
  
  
  RESULTS
  rs17684886 in ZNRF1 and rs599019 near COLEC12 were associated with diabetic retinopathy (OR 0.812, p = 0.0039 and OR 0.835, p = 0.0116, respectively) and with the severity of diabetic retinopathy (p = 0.0365 and p = 0.0252, respectively, for trend analysis). Sub-analysis in patients with diabetic retinopathy revealed that rs6427247 near SCYL1BP1 (also known as GORAB) and rs899036 near API5 were associated with severe diabetic retinopathy (OR 1.368, p = 0.0333 and OR 0.340, p = 0.0005, respectively). The associations between rs6427247 and rs899036 and severe diabetic retinopathy became more evident after a meta-analysis of published GWAS data (OR 1.577, p = 2.01 × 10(-4) for rs6427247; OR 0.330, p = 5.84 × 10(-7) for rs899036).
  
  
  CONCLUSIONS
  We determined that rs17684886 and rs599019 are associated with diabetic retinopathy and that rs6427247 and rs899036 are associated with severe diabetic retinopathy in Chinese patients with type 2 diabetes.
authors.affiliation: Shanghai Diabetes Institute, Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Clinical Center for Diabetes, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, 600 Yishan Road, Shanghai, 200233, People's Republic of China.
authors.forename: Danfeng
authors.initials: D
authors.lastname: Peng
authors.forename: Jie
authors.initials: J
authors.lastname: Wang
authors.forename: Rong
authors.initials: R
authors.lastname: Zhang
authors.forename: Feng
authors.initials: F
authors.lastname: Jiang
authors.forename: Shanshan
authors.initials: S
authors.lastname: Tang
authors.forename: Miao
authors.initials: M
authors.lastname: Chen
authors.forename: Jing
authors.initials: J
authors.lastname: Yan
authors.forename: Xue
authors.initials: X
authors.lastname: Sun
authors.forename: Shiyun
authors.initials: S
authors.lastname: Wang
authors.forename: Tao
authors.initials: T
authors.lastname: Wang
authors.forename: Dandan
authors.initials: D
authors.lastname: Yan
authors.forename: Yuqian
authors.initials: Y
authors.lastname: Bao
authors.forename: Cheng
authors.initials: C
authors.lastname: Hu
authors.forename: Weiping
authors.initials: W
authors.lastname: Jia
mesh_terms: D000368:Aged; D000483:Alleles; D051017:Apoptosis Regulatory Proteins / Q000235:genetics; D044466:Asian People / Q000235:genetics; D002352:Carrier Proteins / Q000235:genetics; D002681:China; D037222:Collectins / Q000235:genetics; D003924:Diabetes Mellitus, Type 2 / Q000208:ethnology* / Q000235:genetics*; D003930:Diabetic Retinopathy / Q000208:ethnology* / Q000235:genetics*; D005260:Female; D005654:Fundus Oculi; D055106:Genome-Wide Association Study; D005838:Genotype; D000077614:Golgi Matrix Proteins; D006801:Humans; D008297:Male; D008875:Middle Aged; D009687:Nuclear Proteins / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D011786:Quality Control; D051116:Receptors, Scavenger / Q000235:genetics; D044767:Ubiquitin-Protein Ligases
chemical_list: C108386:API5 protein, human; D051017:Apoptosis Regulatory Proteins; C422442:COLEC12 protein, human; D002352:Carrier Proteins; D037222:Collectins; C533680:GORAB protein, human; D000077614:Golgi Matrix Proteins; D009687:Nuclear Proteins; D051116:Receptors, Scavenger; D044767:Ubiquitin-Protein Ligases; C544744:ZNRF1 protein, human
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