title: Plasma endothelin-1 and single nucleotide polymorphisms ofendothelin-1 and endothelin type A receptor genesas risk factors for normal tension glaucoma.
abstract: The purpose of this study was to determine whether four single nucleotide polymorphisms (SNPs) ofendothelin and endothelin receptor type A genescan constitute a risk factor for normal tension glaucoma (NTG) and high tension glaucoma (HTG).
  
  
  
  The study included 160 patients with NTG, 124 patients with HTG, and 165 healthy controls. To analyze the frequency of polymorphic variants of theendothelin EDN gene(K198N) and theendothelin receptor type A gene EDN RA(C1222T, C70G, G231A), DNA was isolated from peripheral blood, and SNP genotyping was performed using the real-time PCR (RT-PCR) method. Plasma endothelin (ET) concentrations were detected using an enzyme immunoassay. Endothelin levels were compared with genotype and allele distributions, patients' clinical status, and various risk factors for NTG.
  
  
  
  There was a significant difference between the patients with NTG and HTG and the controls (p = 0.035, p = 0.008) regarding the genotype of the C1222T and C70G polymorphism. Plasma concentrations of ET did not differ between the NTG and HTG groups, and no significant correlation with intraocular pressure (IOP), best-corrected visual acuity (BCVA), and the cup to disc ratio (c/d ratio) was seen in patients with NTG. Plasma endothelin levels showed a noticeably positive correlation with age in the NTG group (R = 0.249, p = 0.042). Higher endothelin levels corresponded to more advanced visual field damage. No statistical difference was observed between variant genotypes of K198N and the ET-1 plasma concentration in patients with NTG, whereas a slightly higher ET level was observed in the patients with HTG with the GT genotype in comparison to those with the GG genotype (p = 0.001). The C1222T polymorphism significantly affected the plasma ET level in patients with NTG. The TT genotype carriers had the highest ET level, and the CC genotype carriers the lowest (p = 0.034). The AA variant genotype of the G231A polymorphism exhibited the highest ET level, while the GG variant genotype represented the lowest level (p = 0.033). No significant differences were observed regarding the endothelin levels and the frequency of notches, peripapillary atrophy, low blood pressure, cold extremities, or migraine in the two groups studied. Slightly lower endothelin plasma levels were observed in patients with optic disc hemorrhages in the NTG group (p = 0.05).
  
  
  
  Polymorphic variants ofendothelin EDN(K198N) andendothelin receptor type A genes EDN RA(C1222T, C70G, G231A) affected ET plasma concentrations. There was no association between the plasma endothelin levels and the risk factors for NTG. According to these results, plasma endothelin concentrations do not appear to be a marker for NTG.
authors: Department of Diagnostics and Microsurgery of Glaucoma, Medical University, Lublin, Poland.
authors: Ewa
authors: E
authors: Kosior-Jarecka
authors: Department of Diagnostics and Microsurgery of Glaucoma, Medical University, Lublin, Poland.
authors: Dominika
authors: D
authors: Wróbel-Dudzińska
authors: Department of Diagnostics and Microsurgery of Glaucoma, Medical University, Lublin, Poland.
authors: Urszula
authors: U
authors: Łukasik
authors: Department of Ophthalmology, National University Health System, National University of Singapore; Singapore Eye Research Institute, Singapore; Singapore National Eye Center, Singapore.
authors: Tin
authors: T
authors: Aung
authors: Genome Institute of Singapore, Singapore; Singapore Eye Research Institute, Singapore, Singapore.
authors: Chiea Chuen
authors: CC
authors: Khor
authors: Department of Clinical Genetics, Medical University, Lublin, Poland.
authors: Janusz
authors: J
authors: Kocki
authors: Department of Diagnostics and Microsurgery of Glaucoma, Medical University, Lublin, Poland.
authors: Tomasz
authors: T
authors: Żarnowski
mesh_terms: D000368:Aged; D019332:Endothelin-1 / Q000097:blood* / Q000235:genetics*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D060005:Genotyping Techniques; D006801:Humans; D007429:Intraocular Pressure; D057066:Low Tension Glaucoma / Q000097:blood / Q000235:genetics*; D008297:Male; D020641:Polymorphism, Single Nucleotide; D060888:Real-Time Polymerase Chain Reaction; D044022:Receptor, Endothelin A / Q000235:genetics*; D012307:Risk Factors; D014792:Visual Acuity
chemical_list: D019332:Endothelin-1; D044022:Receptor, Endothelin A