title: Association of guanosine triphosphate cyclohydrolase 1 gene polymorphisms with fibromyalgia syndrome in a Korean population.
abstract: OBJECTIVE
  Guanosine triphosphate cyclohydrolase 1 (GCH1) is the rate-limiting enzyme in the synthesis of tetrahydrobiopterin, which is an essential cofactor in nitric oxide (NO) production. Polymorphisms in the GCH1 gene have been implicated in protection against pain sensitivity. The aim of our study was to determine whether single-nucleotide polymorphisms (SNP) in the GCH1 gene affect susceptibility and/or pain sensitivity in fibromyalgia syndrome (FM).
  
  
  METHODS
  A total of 409 patients with FM and 422 controls were enrolled. The alleles and genotypes at 4 positions [rs3783641(T>A), rs841(C>T), rs752688(C>T), and rs4411417(T>C)] in the GCH1 gene were analyzed. The associations of the GCH1 SNP with susceptibility and clinical measures in patients with FM were assessed.
  
  
  RESULTS
  The frequencies of alleles and genotypes of the 4 SNP did not differ between patients with FM and healthy controls. Among 13 constructed haplotypes, we further examined 4 (CCTT, TTCT, TTCA, and CCTA) with > 1% frequency in both FM and controls. No associations of GCH1 polymorphisms with FM-related activity or severity indexes were found, although the number and total score of tender points in patients with FM differed among the 4 haplotypes (p = 0.03 and p = 0.01, respectively). The CCTA haplotype of GCH1 was associated with significantly lower pain sensitivity and occurred less frequently than the CCTT haplotype in patients with FM (p = 0.04, OR 0.45, 95% CI 0.21-0.96).
  
  
  CONCLUSIONS
  Our study provides evidence that certain GCH1 haplotypes may be protective against susceptibility and pain sensitivity in FM. Our data suggest that NO is responsible for pain sensitivity in the pathogenesis of FM.
authors: Division of Rheumatology, Department of Internal Medicine, Arthritis and Autoimmunity Research Center, Catholic University of Daegu School of Medicine, Daegu, Korea.
authors: Seong-Kyu
authors: SK
authors: Kim
authors: Seong-Ho
authors: SH
authors: Kim
authors: Seong-Su
authors: SS
authors: Nah
authors: Ji Hyun
authors: JH
authors: Lee
authors: Seung-Jae
authors: SJ
authors: Hong
authors: Hyun-Sook
authors: HS
authors: Kim
authors: Hye-Soon
authors: HS
authors: Lee
authors: Hyoun Ah
authors: HA
authors: Kim
authors: Chung-Il
authors: CI
authors: Joung
authors: Jisuk
authors: J
authors: Bae
authors: Jung-Yoon
authors: JY
authors: Choe
authors: Shin-Seok
authors: SS
authors: Lee
mesh_terms: D000328:Adult; D000483:Alleles; D044466:Asian People; D005260:Female; D005356:Fibromyalgia / Q000235:genetics*; D006136:GTP Cyclohydrolase / Q000235:genetics*; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D008297:Male; D008875:Middle Aged; D017288:Pain Threshold / Q000502:physiology; D020641:Polymorphism, Single Nucleotide; D056910:Republic of Korea
chemical_list: D006136:GTP Cyclohydrolase