title: Regulatory SNPs Alter the Gene Expression of Diabetic Retinopathy Associated Secretary Factors.
abstract: OBJECTIVE
  Diabetic retinopathy (DR) is a common microvascular complication in both type I and type II diabetes. Several previous reports indicated the serum centration of some secretary factors were highly associated with DR. Therefore, we hypothesis regulatory SNPs (rSNPs) genotype in secretary factors may alter these gene expression and lead to DR.
  
  
  METHODS
  At first, pyrosequencing were applying to screen the SNPs which present allele frequency different in DR and DNR. Then individual genotyping was processed by Taqman assays in Taiwanese DR and DNR patients. To evaluate the effect of SNP allele on transcriptional activity, we measured promoter activity using luciferase reporter constructs.
  
  
  RESULTS
  We found the frequencies of the CC, CG, and GG genotype of the rs2010963 polymorphism were 15.09%, 47.14%, and 37.74% in DR and 12.90%, 19.35%, and 67.74% in DNR, respectively (p = 0.0205). The prevalence of DR was higher (p = 0.00793) in patients with the CC or CG genotype (62.26% and 32.26% for DR and DNR, respectively) compared with the patients with the GG genotype. To evaluate the effect of rs2010963-C allele on transcriptional activity, we measured promoter activity using luciferase reporter constructs. The rs2010963-C reporter showed 1.6 to 2-fold higher luciferase activity than rs2010963-G in 3 cell lines.
  
  
  CONCLUSIONS
  Our data proposed rs2010963-C altered the expression level of VEGFA in different tissues. We suggested small increase but long term exposure to VEGFA may lead to DR finally.
authors.affiliation: VYM Genome Research Center, National Yang-Ming University, Taipei, Taiwan;
authors.forename: Chian-Feng
authors.initials: CF
authors.lastname: Chen
authors.affiliation: Department of Ophthalmology, Taipei City Hospital, Taipei, Taiwan;; Department of Ophthalmology, Shin Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan;; Department of Ophthalmology, Taipei Medical University, Taipei, Taiwan;; Department of Ophthalmology, Taiwan University Hospital, Taipei, Taiwan;
authors.forename: Shiow-Wen
authors.initials: SW
authors.lastname: Liou
authors.affiliation: VYM Genome Research Center, National Yang-Ming University, Taipei, Taiwan;
authors.forename: Hsin-Han
authors.initials: HH
authors.lastname: Wu
authors.affiliation: VYM Genome Research Center, National Yang-Ming University, Taipei, Taiwan;
authors.forename: Chin-Hui
authors.initials: CH
authors.lastname: Lin
authors.affiliation: Department of Internal Medicine, Taipei City Hospital, Taipei, Taiwan;
authors.forename: Li-Shan
authors.initials: LS
authors.lastname: Huang
authors.affiliation: Department of Ophthalmology, Taipei City Hospital, Taipei, Taiwan;; Department of Ophthalmology, Taiwan University Hospital, Taipei, Taiwan;; Department of Health Care Management, National Taipei University of Nursing and Health Sciences, Taipei, Taiwan;; Department of Medicine, National Yang-Ming University, Taipei, Taiwan;; Institute of Public Health, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Lin-Chung
authors.initials: LC
authors.lastname: Woung
authors.affiliation: Department of Ophthalmology, Taipei City Hospital, Taipei, Taiwan;; Institute of Public Health, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Ching-Yao
authors.initials: CY
authors.lastname: Tsai
mesh_terms: D000328:Adult; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000235:genetics* / Q000473:pathology; D003930:Diabetic Retinopathy / Q000235:genetics* / Q000473:pathology; D005260:Female; D005786:Gene Expression Regulation; D005787:Gene Frequency; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012045:Regulatory Sequences, Nucleic Acid / Q000235:genetics*; D012307:Risk Factors; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis / Q000235:genetics*
chemical_list: C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A
keywords: DR; SNP; VEGFA.