title: Corticotropin-releasing hormone receptor 1 gene variants in irritable bowel syndrome.
abstract: BACKGROUND
  Corticotropin-releasing hormone (CRH) acts mainly via the CRH receptor 1 (CRH-R1) and plays a crucial role in the stress-induced pathophysiology of irritable bowel syndrome (IBS). Several studies have demonstrated that variants of the CRH-R1 gene carry a potential risk for depression, but evidence for an association between CRH-R1 genotypes and IBS is lacking. We tested the hypothesis that genetic polymorphisms and haplotypes of CRH-R1 moderate the IBS phenotype and negative emotion in IBS patients.
  
  
  METHODS
  A total of 103 patients with IBS and 142 healthy controls participated in the study. Three single-nucleotide polymorphisms of the CRH-R1 gene (rs7209436, rs242924, and rs110402) were genotyped. Subjects' emotional states were evaluated using the Perceived-Stress Scale, the State-Trait Anxiety Inventory, and the Self-rating Depression Scale.
  
  
  RESULTS
  The TT genotype of rs7209436 (P = 0.01) and rs242924 (P = 0.02) was significantly more common in patients with IBS than in controls. Total sample analysis showed significant association between bowel pattern (normal, diarrhea, constipation, or mixed symptoms) and the T allele of rs7209436 (P = 0.008), T allele of rs242924 (P = 0.019), A allele of rs110402 (P = 0.047), and TAT haplocopies (P = 0.048). Negative emotion was not associated with the examined CRH-R1 SNPs.
  
  
  CONCLUSIONS
  These findings suggest that genetic polymorphisms and the CRH-R1 haplotypes moderate IBS and related bowel patterns. There was no clear association between CRH-R1 genotypes and negative emotion accompanying IBS. Further studies on the CRH system are therefore warranted.
authors.affiliation: Department of Behavioral Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors.forename: Naoko
authors.initials: N
authors.lastname: Sato
authors.forename: Naoki
authors.initials: N
authors.lastname: Suzuki
authors.forename: Ayaka
authors.initials: A
authors.lastname: Sasaki
authors.forename: Emiko
authors.initials: E
authors.lastname: Aizawa
authors.forename: Takeshi
authors.initials: T
authors.lastname: Obayashi
authors.forename: Motoyori
authors.initials: M
authors.lastname: Kanazawa
authors.forename: Tomoko
authors.initials: T
authors.lastname: Mizuno
authors.forename: Michiko
authors.initials: M
authors.lastname: Kano
authors.forename: Masashi
authors.initials: M
authors.lastname: Aoki
authors.forename: Shin
authors.initials: S
authors.lastname: Fukudo
mesh_terms: D000328:Adult; D001007:Anxiety / Q000150:complications; D016022:Case-Control Studies; D003863:Depression / Q000150:complications; D004644:Emotions; D005260:Female; D005786:Gene Expression Regulation; D014644:Genetic Variation; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D043183:Irritable Bowel Syndrome / Q000235:genetics* / Q000378:metabolism / Q000523:psychology; D008297:Male; D010641:Phenotype; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D018019:Receptors, Corticotropin-Releasing Hormone / Q000235:genetics*; D012306:Risk; D000099052:CRF Receptor, Type 1
chemical_list: D018019:Receptors, Corticotropin-Releasing Hormone; D000099052:CRF Receptor, Type 1