title: Lack of influence of GTP cyclohydrolase gene (GCH1) variations on pain sensitivity in humans.
abstract: OBJECTIVE
  To assess the effect of variations in GTP cyclohydrolase gene (GCH1) on pain sensitivity in humans.
  
  
  METHODS
  Thermal and cold pain sensitivity were evaluated in a cohort of 735 healthy volunteers. Among this cohort, the clinical pain responses of 221 subjects after the surgical removal of impacted third molars were evaluated. Genotyping was done for 38 single nucleotide polymorphisms (SNPs) whose heterozygosity > 0.2 in GCH1. Influence of the genetic variations including SNPs and haplotypes on pain sensitivity were analyzed.
  
  
  RESULTS
  Minor allele frequencies and linkage disequilibrium show significant differences in European Americans, African Americans, Hispanic Americans and Asian Americans. Association analyses in European Americans do not replicate the previously reported important influence of GCH1 variations on pain sensitivity.
  
  
  CONCLUSIONS
  Considering population stratification, previously reported associations between GCH1 genetic variations and pain sensitivity appear weak or negligible in this well characterized model of pain.
authors.affiliation: National Institute of Nursing Research, National Institutes of Health, Bethesda, MD, USA. kimhy@mail.nih.gov
authors.forename: Hyungsuk
authors.initials: H
authors.lastname: Kim
authors.forename: Raymond A
authors.initials: RA
authors.lastname: Dionne
mesh_terms: D015331:Cohort Studies; D005260:Female; D006136:GTP Cyclohydrolase / Q000235:genetics*; D005787:Gene Frequency; D014644:Genetic Variation; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D010146:Pain / Q000201:enzymology / Q000235:genetics*; D017288:Pain Threshold; D020641:Polymorphism, Single Nucleotide
chemical_list: D006136:GTP Cyclohydrolase