title: GTP cyclohydrolase I gene polymorphisms are associated with endothelial dysfunction and oxidative stress in patients with type 2 diabetes mellitus.
abstract: BACKGROUND
  The genetic background of atherosclerosis in type 2 diabetes mellitus (T2DM) is complex and poorly understood. Studying genetic components of intermediate phenotypes, such as endothelial dysfunction and oxidative stress, may aid in identifying novel genetic components for atherosclerosis in diabetic patients.
  
  
  METHODS
  Five polymorphisms forming two haplotype blocks within the GTP cyclohydrolase 1 gene, encoding a rate limiting enzyme in tetrahydrobiopterin synthesis, were studied in the context of flow and nitroglycerin mediated dilation (FMD and NMD), intima-media thickness (IMT), and plasma concentrations of von Willebrand factor (vWF) and malondialdehyde (MDA).
  
  
  RESULTS
  Rs841 was associated with FMD (p = 0.01), while polymorphisms Rs10483639, Rs841, Rs3783641 (which form a single haplotype) were associated with both MDA (p = 0.012, p = 0.0015 and p = 0.003, respectively) and vWF concentrations (p = 0.016, p = 0.03 and p = 0.045, respectively). In addition, polymorphism Rs8007267 was also associated with MDA (p = 0.006). Haplotype analysis confirmed the association of both haplotypes with studied variables.
  
  
  CONCLUSIONS
  Genetic variation of the GCH1 gene is associated with endothelial dysfunction and oxidative stress in T2DM patients.
authors.affiliation: Centre for Medical Genomics OMICRON, Jagiellonian University Medical College, Krakow, Poland; Department of Pharmacology, Jagiellonian University Medical College, Krakow, Poland.
authors.forename: Pawel P
authors.initials: PP
authors.lastname: Wolkow
authors.affiliation: Department of Internal and Agricultural Medicine, Jagiellonian University Medical College, Krakow, Poland.
authors.forename: Wladyslaw
authors.initials: W
authors.lastname: Kosiniak-Kamysz
authors.affiliation: Department of Internal and Agricultural Medicine, Jagiellonian University Medical College, Krakow, Poland.
authors.forename: Grzegorz
authors.initials: G
authors.lastname: Osmenda
authors.affiliation: Department of Internal and Agricultural Medicine, Jagiellonian University Medical College, Krakow, Poland.
authors.forename: Grzegorz
authors.initials: G
authors.lastname: Wilk
authors.affiliation: Centre for Medical Genomics OMICRON, Jagiellonian University Medical College, Krakow, Poland; Department of Pharmacology, Jagiellonian University Medical College, Krakow, Poland.
authors.forename: Beata
authors.initials: B
authors.lastname: Bujak-Gizycka
authors.affiliation: Department of Internal and Agricultural Medicine, Jagiellonian University Medical College, Krakow, Poland.
authors.forename: Adam
authors.initials: A
authors.lastname: Ignacak
authors.affiliation: Department of Clinical Pharmacology, Vanderbilt University, Nashville, TN, United States of America.
authors.forename: Mihir
authors.initials: M
authors.lastname: Kanitkar
authors.affiliation: Department of Metabolic Diseases, Jagiellonian University Medical College, Krakow, Poland.
authors.forename: Malgorzata
authors.initials: M
authors.lastname: Walus-Miarka
authors.affiliation: Department of Clinical Pharmacology, Vanderbilt University, Nashville, TN, United States of America.
authors.forename: David G
authors.initials: DG
authors.lastname: Harrison
authors.affiliation: Department of Pharmacology, Jagiellonian University Medical College, Krakow, Poland.
authors.forename: Ryszard
authors.initials: R
authors.lastname: Korbut
authors.affiliation: Department of Metabolic Diseases, Jagiellonian University Medical College, Krakow, Poland; University Hospital, Krakow, Poland.
authors.forename: Maciej T
authors.initials: MT
authors.lastname: Malecki
authors.affiliation: Department of Internal and Agricultural Medicine, Jagiellonian University Medical College, Krakow, Poland; Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, United Kingdom.
authors.forename: Tomasz J
authors.initials: TJ
authors.lastname: Guzik
mesh_terms: D020413:3' Untranslated Regions; D000328:Adult; D000368:Aged; D000483:Alleles; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics* / Q000473:pathology; D004730:Endothelium, Vascular / Q000201:enzymology*; D005260:Female; D006136:GTP Cyclohydrolase / Q000235:genetics*; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D008315:Malondialdehyde / Q000097:blood; D008875:Middle Aged; D018384:Oxidative Stress / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D014841:von Willebrand Factor / Q000032:analysis / Q000235:genetics
chemical_list: D020413:3' Untranslated Regions; D014841:von Willebrand Factor; D008315:Malondialdehyde; D006136:GTP Cyclohydrolase