Cannabinoid Receptor 1 Gene Polymorphism And Irritable Bowel Syndrome

Background Irritable bowel syndrome (IBS) is one of the most common diseases in functional bowel diseases with high prevalence and great difficulties in treatment. Though it has been found that the most important pathophysiologic changes in IBS are visceral hypersensitivity and motility dysfunction, it's pathogenesis is still unclear. The cannabinoids affect gastrointestinal function and are thought to be involved in the pathogenesis of IBS. We hypothesized that genetic variants of the cannabinoid receptor 1 gene (CNR1) might be associated with IBS. To our knowledge, there is no study of the association between CNR1 gene polymorphism and IBS. This study is to investigate the genetic association of CNR1 gene polymorphisms in healthy adults and patients with IBS.Objectives To investigate the gene polymorphism of AAT triplet repeats in the 3′-flanking region of the CNR1 gene, and their relationship to IBS.Methods①Polymerase chain reaction (PCR) was used to detect the CNR1 gene expressions in 115 patients with IBS confirmed with RomeⅢcriteria and 95 healthy subjects.②All PCR fragments were sequenced to investigate the number variants of AAT triplet repeats in the 3′-flanking region of the CNR1 gene.Results①Eight allele frequencies and 20 genotypes of CNR1 were detected. The most common allele frequency was (AAT)13 in both IBS group and control group (48.23% vs 42.6%). The major genotypes was 13/13 in the IBS group(24.3%) and in control group(21.3%). we divided these 8 alleles into two groups comprising shorter alleles (<10 repeats) and longer alleles (≥10 repeats). This produced three CNR1 genotypes <10/<10,<10/≥10 and≥10/≥10. The <10/<10, <10/≥10 and≥10/≥10 genotypes in IBS patients were 0%,5.2%,and 94.8%, and their corresponding in healthy controls were 1.1%,12.6%,and 86.3%, respectively.The allele frequencies of <10 and≥10 in patients with IBS were 2.6% and 97.4%, while were 7.4% and 92.6% in controls.②T he CNR1 having≥10 AAT triplet repeats occurred with greater frequency in IBS patients than in the controls (χ2 =5.198,P=0.023); The frequency of the≥10 repeat alleles were increased in IBS-D subtypes than in controls, although there were no significant differences (P=0.051). There were significant differences between IBS patients and controls on genotypes of≥10/≥10 (94.8% vs 86.3%,χ2=4.532, P=0.033). IBS subgroup analysis showed that the frequency of the≥10/≥10 genotype was higher in IBS-D subtypes (95.3%) than in controls (86.3%), although there were no significant differences (P=0.064). When divided subjects with IBS patients and controls according to gender, we found that allele frequencies≥10 were significant higher in IBS group than in control group in men (P=0.045). The same trend was also found in IBS-D male subjects (P=0.055). The frequency of the≥10/≥10 genotype was higher in IBS male subtypes than in male controls, although there were no significant differences (P=0.072). The male patients with IBS-D showed a tendency of having high percentage of genotype≥10/≥10 than in controlled group,but no reaching a significant difference (P=0.090).Conclusions①The most common allele frequency was (AAT)13, and the major genotype was 13/13 in Guangdong Han Population;②The CNR1 gene polymorphism were partly associated with the etiology of IBS. The presence of allele frequencies≥10 and≥10/≥10 genotype had an increased risk of development of IBS-D in men.