title: Impact of Genetic Loci Identified in Genome-Wide Association Studies on Diabetic Retinopathy in Chinese Patients With Type 2 Diabetes.
abstract: OBJECTIVE
  Diabetic retinopathy (DR) is a common microvascular complication of type 2 diabetes (T2DM). Genome-wide association studies (GWAS) had identified novel DR-susceptibility genetic variants in various populations. We examined the associations of these DR-associated single nucleotide polymorphisms (SNPs) with severe DR in a Chinese T2DM cohort.
  
  
  METHODS
  Cross-sectional case-control studies on sight-threatening DR (STDR) and proliferative DR (PDR) were performed. We genotyped 38 SNPs showing top association signals with DR in previous GWAS in 567 STDR cases, including 309 with PDR and 1490 non-DR controls. Multiple logistic regression models with adjustment for conventional risk factors, including age, sex, duration of diabetes, and presence of hypertension, were employed.
  
  
  RESULTS
  The strongest association was found at INSR rs2115386, an intronic SNP of INSR: Padjusted = 9.13 × 10-4 (odds ratio [OR],1.28; 95% confidence interval [95%CI], 1.11-1.48) for STDR, and Padjusted= 1.12 × 10-4 (OR [95%CI],1.44 [1.20-1.74]) for PDR. rs599019 located downstream of COLEC12 (Padjusted = 0.019; OR [95%CI],1.19 [1.03-1.38]) and rs4462262 located at an intergenic region between ZWINT and MRPS35P3 (Padjusted = 0.041; OR [95%CI],1.38[1.01-1.89]) also were significantly associated with STDR, but not with PDR alone. On the other hand, MYT1L-LOC729897 rs10199521 (Padjusted = 0.022; OR [95%CI],1.25 [1.03-1.51]) and API5 rs899036 (Padjusted = 0.049; OR [95%CI],1.36 [1.00-1.85]) showed significant independent associations only with PDR. Similar results were obtained when hemoglobin A1c also was included in the adjustment models.
  
  
  CONCLUSIONS
  We demonstrated the significant and independent associations of several GWAS-identified SNPs with DR in Chinese T2DM patients with severe DR. The findings on INSR rs2115386 are supportive of the role of insulin resistance, or the compensatory hyperinsulinemia, in the pathogenesis of DR.
authors: Department of Medicine, The University of Hong Kong, Hong Kong.
authors: Chloe Y Y
authors: CY
authors: Cheung
authors: Department of Medicine, The University of Hong Kong, Hong Kong.
authors: Elaine Y L
authors: EY
authors: Hui
authors: Department of Medicine, The University of Hong Kong, Hong Kong.
authors: Chi-Ho
authors: CH
authors: Lee
authors: Department of Medicine, The University of Hong Kong, Hong Kong.
authors: Kelvin H M
authors: KH
authors: Kwok
authors: Department of Ophthalmology, The University of Hong Kong, Hong Kong.
authors: Rita A
authors: RA
authors: Gangwani
authors: Department of Ophthalmology, United Christian Hospital, Hong Kong.
authors: Kenneth K W
authors: KK
authors: Li
authors: Department of Ophthalmology, United Christian Hospital, Hong Kong.
authors: Jeffrey C W
authors: JC
authors: Chan
authors: Department of Medicine, The University of Hong Kong, Hong Kong.
authors: Yu-Cho
authors: YC
authors: Woo
authors: Department of Medicine, The University of Hong Kong, Hong Kong.
authors: Wing-Sun
authors: WS
authors: Chow
authors: Department of Medicine, The University of Hong Kong, Hong Kong.
authors: Michele M A
authors: MM
authors: Yuen
authors: Department of Medicine, The University of Hong Kong, Hong Kong.
authors: Rachel L C
authors: RL
authors: Wong
authors: Department of Medicine, The University of Hong Kong, Hong Kong.
authors: Carol H Y
authors: CH
authors: Fong
authors: Department of Medicine, The University of Hong Kong, Hong Kong 4Research Center of Heart, Brain, Hormone and Healthy Aging, The University of Hong Kong, Hong Kong 5State Key Laboratory of Pharmaceutical Biotechnology, The University of Hong Kong, Hong Kong.
authors: Aimin
authors: A
authors: Xu
authors: Department of Ophthalmology, The University of Hong Kong, Hong Kong.
authors: David S H
authors: DS
authors: Wong
authors: Department of Psychiatry, The University of Hong Kong, Hong Kong 7Center for Genomic Sciences, The University of Hong Kong, Hong Kong.
authors: Pak-Chung
authors: PC
authors: Sham
authors: Department of Medicine, The University of Hong Kong, Hong Kong 4Research Center of Heart, Brain, Hormone and Healthy Aging, The University of Hong Kong, Hong Kong 5State Key Laboratory of Pharmaceutical Biotechnology, The University of Hong Kong, Hong Kong.
authors: Karen S L
authors: KS
authors: Lam
mesh_terms: D002681:China / Q000453:epidemiology; D003430:Cross-Sectional Studies; D003924:Diabetes Mellitus, Type 2 / Q000150:complications* / Q000453:epidemiology / Q000235:genetics; D003930:Diabetic Retinopathy / Q000453:epidemiology / Q000209:etiology / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D056426:Genetic Loci / Q000235:genetics*; D055106:Genome-Wide Association Study / Q000379:methods*; D005838:Genotype; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide; D012189:Retrospective Studies