title: Corticotropin-Releasing Hormone Receptor 2 Gene Variants in Irritable Bowel Syndrome.
abstract: BACKGROUND
  Corticotropin-releasing hormone (CRH) plays an important role in the pathophysiology of irritable bowel syndrome (IBS) and regulates the stress response through two CRH receptors (R1 and R2). Previously, we reported that a CRHR1 gene polymorphism (rs110402, rs242924, and rs7209436) and haplotypes were associated with IBS. However, the association between the CRHR2 gene and IBS was not investigated. We tested the hypothesis that genetic polymorphisms and haplotypes of CRHR2 are associated with IBS pathophysiology and negative emotion in IBS patients.
  
  
  METHODS
  A total of 142 IBS patients and 142 healthy controls participated in this study. Seven single nucleotide polymorphisms (SNPs) of the CRHR2 gene (rs4722999, rs3779250, rs2240403, rs2267710, rs2190242, rs2284217, and rs2284220) were genotyped. Subjects' psychological states were evaluated using the Perceived-Stress Scale, the State-Trait Anxiety Inventory, and the Self-Rating Depression Scale.
  
  
  RESULTS
  We found that rs4722999 and rs3779250, located in intronic region, were associated with IBS in terms of genotype frequency (rs4722999: P = 0.037; rs3779250: P = 0.017) and that the distribution of the major allele was significantly different between patients and controls. There was a significant group effect (controls vs. IBS), and a CRHR2 genotype effect was observed for three psychological scores, but the interaction was not significant. We found a haplotype of four SNPs (rs4722999, rs3779250, rs2240403, and rs2267710) and two SNPs (rs2284217 and rs2284220) in strong linkage disequilibrium (D' > 0.90). We also found that haplotypes of the CRHR2 gene were significantly different between IBS patients and controls and that they were associated with negative emotion.
  
  
  CONCLUSIONS
  Our findings support the hypothesis that genetic polymorphisms and haplotypes of CRHR2 are related to IBS. In addition, we found associations between CRHR2 genotypes and haplotypes and negative emotion in IBS patients and controls. Further studies on IBS and the CRH system are warranted.
authors.affiliation: Department of Behavioral Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors.forename: Hazuki
authors.initials: H
authors.lastname: Komuro
authors.affiliation: Department of Behavioral Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors.forename: Naoko
authors.initials: N
authors.lastname: Sato
authors.affiliation: Department of Behavioral Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors.forename: Ayaka
authors.initials: A
authors.lastname: Sasaki
authors.affiliation: Department of Neurology, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors.forename: Naoki
authors.initials: N
authors.lastname: Suzuki
authors.affiliation: Department of Behavioral Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan.|Frontier Research Institute for Interdisciplinary Sciences, Tohoku University, Sendai, Japan.
authors.forename: Michiko
authors.initials: M
authors.lastname: Kano
authors.affiliation: Department of Behavioral Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan.|Department of Integrative Genomics, Tohoku Medical Megabank Organization, Tohoku University, Sendai, Japan.
authors.forename: Yukari
authors.initials: Y
authors.lastname: Tanaka
authors.affiliation: Department of Integrative Genomics, Tohoku Medical Megabank Organization, Tohoku University, Sendai, Japan.|Graduate School of Medicine, Tohoku University, Sendai, Japan.
authors.forename: Yumi
authors.initials: Y
authors.lastname: Yamaguchi-Kabata
authors.affiliation: Department of Behavioral Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors.forename: Motoyori
authors.initials: M
authors.lastname: Kanazawa
authors.affiliation: Department of Neurology, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Warita
authors.affiliation: Department of Neurology, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors.forename: Masashi
authors.initials: M
authors.lastname: Aoki
authors.affiliation: Department of Behavioral Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan.|Department of Psychosomatic Medicine, Tohoku University Hospital, Sendai, Japan.
authors.forename: Shin
authors.initials: S
authors.lastname: Fukudo
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D043183:Irritable Bowel Syndrome / Q000235:genetics*; D008297:Male; D020641:Polymorphism, Single Nucleotide; D018019:Receptors, Corticotropin-Releasing Hormone / Q000235:genetics*; D055815:Young Adult
chemical_list: C101531:CRF receptor type 2; D018019:Receptors, Corticotropin-Releasing Hormone