TY - JOUR
T1 - Associations between single-nucleotide polymorphisms in corticotropin-releasing hormone-related genes and Irritable bowel syndrome
AU - Sasaki, Ayaka
AU - Sato, Naoko
AU - Suzuki, Naoki
AU - Kano, Michiko
AU - Tanaka, Yukari
AU - Kanazawa, Motoyori
AU - Aoki, Masashi
AU - Fukudo, Shin
N1 - Publisher Copyright:
© 2016 Sasaki et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
PY - 2016/2
Y1 - 2016/2
N2 - Irritable bowel syndrome (IBS) is a common functional disorder with distinct features of stress-related pathophysiology. A key mediator of the stress response is corticotropinreleasing hormone (CRH). Although some candidate genes have been identified in stressrelated disorders, few studies have examined CRH-related gene polymorphisms. Therefore, we tested our hypothesis that single-nucleotide polymorphisms (SNPs) in CRH-related genes influence the features of IBS. Methods: In total, 253 individuals (123 men and 130 women) participated in this study. They comprised 111 IBS individuals and 142 healthy controls. The SNP genotypes in CRH (rs28364015 and rs6472258) and CRH-binding protein (CRH-BP) (rs10474485) were determined by direct sequencing and real-time polymerase chain reaction. The emotional states of the subjects were evaluated using the State-Trait Anxiety Inventory, Perceived Stress Scale, and the Self-rating Depression Scale. Results: Direct sequencing of the rs28364015 SNP of CRH revealed no genetic variation among the study subjects. There was no difference in the genotype distributions and allele frequencies of rs6472258 and rs10474485 between IBS individuals and controls. However, IBS subjects with diarrhea symptoms without the rs10474485 A allele showed a significantly higher emotional state score than carriers. Conclusions: These results suggest that the CRH and CRHBP genes have no direct effect on IBS status. However, the CRH-BP SNP rs10474485 has some effect on IBS-related emotional abnormalities and resistance to psychosocial stress.
AB - Irritable bowel syndrome (IBS) is a common functional disorder with distinct features of stress-related pathophysiology. A key mediator of the stress response is corticotropinreleasing hormone (CRH). Although some candidate genes have been identified in stressrelated disorders, few studies have examined CRH-related gene polymorphisms. Therefore, we tested our hypothesis that single-nucleotide polymorphisms (SNPs) in CRH-related genes influence the features of IBS. Methods: In total, 253 individuals (123 men and 130 women) participated in this study. They comprised 111 IBS individuals and 142 healthy controls. The SNP genotypes in CRH (rs28364015 and rs6472258) and CRH-binding protein (CRH-BP) (rs10474485) were determined by direct sequencing and real-time polymerase chain reaction. The emotional states of the subjects were evaluated using the State-Trait Anxiety Inventory, Perceived Stress Scale, and the Self-rating Depression Scale. Results: Direct sequencing of the rs28364015 SNP of CRH revealed no genetic variation among the study subjects. There was no difference in the genotype distributions and allele frequencies of rs6472258 and rs10474485 between IBS individuals and controls. However, IBS subjects with diarrhea symptoms without the rs10474485 A allele showed a significantly higher emotional state score than carriers. Conclusions: These results suggest that the CRH and CRHBP genes have no direct effect on IBS status. However, the CRH-BP SNP rs10474485 has some effect on IBS-related emotional abnormalities and resistance to psychosocial stress.
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U2 - 10.1371/journal.pone.0149322
DO - 10.1371/journal.pone.0149322
M3 - Article
C2 - 26882083
AN - SCOPUS:84960502854
VL - 11
JO - PLoS One
JF - PLoS One
SN - 1932-6203
IS - 2
M1 - e0149322
ER -