AbstractBackground and AimThe endocannabinoid system is involved in the pathophysiology of irritable bowel syndrome (IBS). Here, we investigated whether genetic variants of the cannabinoid type 1 receptor (CNR1) and fatty acid amide hydrolase (FAAH) are associated with the pathogenesis of IBS.MethodsIn total, 292 patients with IBS and 298 healthy controls were enrolled. Polymerase chain reaction (PCR) and DNA sequencing were applied to determine the genotyping of polymorphic triplet AAT repeats located at the 3′‐end of the CNR1 gene. The single nucleotide polymorphism (SNP) C385A at the FAAH gene (rs324420) was determined by PCR using TaqMan SNP Genotyping Assay Sets.ResultsA total of eight alleles with AAT triplet repeats in the CNR1 gene were detected. The alleles were divided into two groups (≤ 10 and > 10) and three genotypes (≤ 10/≤ 10, ≤ 10/> 10, and > 10/> 10). The frequency of > 10 alleles was significantly higher in the IBS group (90.6%) when compared with the control group {81.7%, P < 0.001, odds ratio (OR) (95% confidence interval [CI]) = −0.128}. In addition, the genotypes > 10/> 10 were significantly associated with IBS (P < 0.001, OR [95% CI] = −0.163). The frequency of the A allele and the distribution of the AA genotype in the FAAH gene in the IBS group were not significantly different from those in the control group (P > 0.05), even though the frequency of the AA genotype was lower in the IBS group (1.0%) than that in the control group (3.4%, P = 0.089, OR [95% CI] = 3.345).ConclusionsThe variation in the (AAT)n repeat of the CNR1 gene conferred an increased risk for developing IBS, while rs324420 (C385) in the FAAH gene was not associated with IBS pathogenesis.