OBJECTIVE: The cannabinoids affect gastrointestinal function and are thought to be involved in the pathogenesis of irritable bowel syndrome (IBS). We hypothesized that genetic variants of the cannabinoid receptor 1 gene (CNR1) might be associated with IBS. METHODS: One hundred sixty-two IBS patients, who met the Rome II criteria, and 423 healthy controls were subjected to genotyping of polymorphic triplet AAT repeats located in the 3-flanking region of the CNR1 gene. RESULTS: Allele frequencies of AAT triplet repeats in the CNR1 gene differed markedly between the controls and IBS patients (P<0.01). Controls had a lower frequency of distribution of 10 alleles or more. We divided the alleles into 2 groups (≤ 10 and >10), and 3 genotypes ≤ 10/≤ 10, heterozygote, and >10/>10. The CNR1 having>10/>10 AAT triplet repeats occurred with greater frequency in IBS patients than in the controls (P<0.01). A strong genotype association was observed between the CNR1 >10/>10 genotype and all IBS subtypes compared with controls (P<0.01 for each). The allele frequencies and the CNR1 genotypes did not differ between the 3 IBS subtypes. Symptom scores for abdominal discomfort or pain were higher in patients with the CNR1 >10/>10 genotype than in patients with the other genotypes (P<0.05). CONCLUSIONS: We found a different distribution of allelic frequency of AAT repeats in the CNR1 gene in healthy controls and IBS patients, and a significant association between the CNR1 >10/>10 genotype and IBS. These results suggest that the CNR1 gene is a potential candidate gene involved in IBS in Korea.
OBJECTIVE: The cannabinoids affect gastrointestinal function and are thought to be involved in the pathogenesis of irritable bowel syndrome (IBS). We hypothesized that genetic variants of the cannabinoid receptor 1 gene (CNR1) might be associated with IBS. METHODS: One hundred sixty-two IBSpatients, who met the Rome II criteria, and 423 healthy controls were subjected to genotyping of polymorphic triplet AAT repeats located in the 3-flanking region of the CNR1 gene. RESULTS: Allele frequencies of AAT triplet repeats in the CNR1 gene differed markedly between the controls and IBSpatients (P<0.01). Controls had a lower frequency of distribution of 10 alleles or more. We divided the alleles into 2 groups (≤ 10 and >10), and 3 genotypes ≤ 10/≤ 10, heterozygote, and >10/>10. The CNR1 having>10/>10 AAT triplet repeats occurred with greater frequency in IBSpatients than in the controls (P<0.01). A strong genotype association was observed between the CNR1 >10/>10 genotype and all IBS subtypes compared with controls (P<0.01 for each). The allele frequencies and the CNR1 genotypes did not differ between the 3 IBS subtypes. Symptom scores for abdominal discomfort or pain were higher in patients with the CNR1 >10/>10 genotype than in patients with the other genotypes (P<0.05). CONCLUSIONS: We found a different distribution of allelic frequency of AAT repeats in the CNR1 gene in healthy controls and IBSpatients, and a significant association between the CNR1 >10/>10 genotype and IBS. These results suggest that the CNR1 gene is a potential candidate gene involved in IBS in Korea.
Authors: Shad B Smith; Dylan W Maixner; Roger B Fillingim; Gary Slade; Richard H Gracely; Kirsten Ambrose; Dmitri V Zaykin; Craig Hyde; Sally John; Keith Tan; William Maixner; Luda Diatchenko Journal: Arthritis Rheum Date: 2012-02
Authors: Anna Vaiopoulou; Georgios Karamanolis; Theodora Psaltopoulou; George Karatzias; Maria Gazouli Journal: World J Gastroenterol Date: 2014-01-14 Impact factor: 5.742
Authors: Michael Camilleri; Gururaj J Kolar; Maria I Vazquez-Roque; Paula Carlson; Duane D Burton; Alan R Zinsmeister Journal: Am J Physiol Gastrointest Liver Physiol Date: 2013-01-10 Impact factor: 4.052