title: EDN1 Lys198Asn is associated with diabetic retinopathy in type 2 diabetes.
abstract: OBJECTIVE
  We tested the hypothesis that genetic variants in vasoactive and angiogenic factors regulating the retina vasculature contribute to the development of diabetic retinopathy (DR).
  
  
  METHODS
  A case-control study was performed to study the genetic association between DR and polymorphic variants of EDN1 (Lys198Asn), LTA (IVS1-80C>A, IVS1-206G>C, IVS1-252A>G), eNOS (Glu298Asp), and ITGA2 (BgI II) in a Chinese population with type 2 diabetes mellitus. A well defined population with type 2 diabetes, consisting of 127 controls and 216 DR patients, was recruited.
  
  
  RESULTS
  A higher frequency of the Asn/Asn genotype of EDN1 was found in individuals with at least 10 years of diabetes and no retinopathy (controls) compared with DR patients with any duration of diabetes (DR: 2.3%; control: 11.0%; p=0.0002). The Asn allele was also more frequent in controls than DR patients (DR: 16.4%; control: 29.5%; p=0.007). Multiple logistic regression analysis showed that the Asn/Asn genotype was the factor most significantly associated with reduced risk of DR (odds ratio=0.19; 95% CI: 0.07-0.53; p=0.002) and with late onset of diabetes (Asn/Asn: 59 years; Lys/Lys + Lys/Asn: 53 years; p=0.02). Moreover, the Lys/Lys genotype was more common among patients with nonproliferative (75.7%) than proliferative DR (56.9%; p=0.008). The distributions of Lys198Asn alleles in hypertension did not differ from normotensive subjects. No associations between DR and polymorphisms of LTA, eNOS, or ITGA2 were detected, and there were no detectable gene-gene or gene-environmental interactions among the polymorphisms.
  
  
  CONCLUSIONS
  The Asn/Asn genotype of EDN1 was associated with a reduced risk of DR and with delayed onset of type 2 diabetes.
authors.affiliation: Department of Ophthalmology and Visual Sciences, The Chinese University of Hong Kong, Kowloon, Hong Kong, China.
authors.forename: Haitao
authors.initials: H
authors.lastname: Li
authors.forename: Janice W C
authors.initials: JW
authors.lastname: Louey
authors.forename: Kwong Wai
authors.initials: KW
authors.lastname: Choy
authors.forename: David T L
authors.initials: DT
authors.lastname: Liu
authors.forename: Wai Man
authors.initials: WM
authors.lastname: Chan
authors.forename: Yiu Man
authors.initials: YM
authors.lastname: Chan
authors.forename: Nicholas S K
authors.initials: NS
authors.lastname: Fung
authors.forename: Bao Jian
authors.initials: BJ
authors.lastname: Fan
authors.forename: Larry
authors.initials: L
authors.lastname: Baum
authors.forename: Juliana C N
authors.initials: JC
authors.lastname: Chan
authors.forename: Dennis S C
authors.initials: DS
authors.lastname: Lam
authors.forename: Chi Pui
authors.initials: CP
authors.lastname: Pang
mesh_terms: D017668:Age of Onset; D000368:Aged; D001216:Asparagine / Q000235:genetics; D016022:Case-Control Studies; D002681:China / Q000453:epidemiology; D003924:Diabetes Mellitus, Type 2 / Q000150:complications* / Q000453:epidemiology / Q000235:genetics*; D003930:Diabetic Retinopathy / Q000150:complications* / Q000235:genetics*; D019332:Endothelin-1 / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D006973:Hypertension / Q000150:complications / Q000235:genetics; D008239:Lysine / Q000235:genetics; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012044:Regression Analysis
chemical_list: D019332:Endothelin-1; D001216:Asparagine; D008239:Lysine