Altered endocannabinoid system gene expression in inflammatory bowel disease mucosa: New perspectives in inflammatory bowel disease management

Table 1 Sociodemographic and clinical data of the individuals involved in the study

Feature	CTRL (n = 17)	IBD (n = 30)	UC (n = 17)	CD (n = 13)	P value
Age	48.12 ± 17.46	49.60 ± 14.53	48.82 ± 11.89	49.31 ± 17.94	P = 0.756 (CTRL vs IBD); P = 0.741 (CTRL vs UC); P = 0.829 (CTRL vs CD)
Sex M, F	52.9% F; 47.1% M	20% F; 80% M	11.76% F; 88.24% M	30.77% F; 69.23% M	P = 0.020; χ2 = 5.419 (CTRL vs IBD); P = 0.026; χ2 = 6.585 (CTRL vs UC); P = 0.283; χ2 = 1.475 (CTRL vs CD)
Disease status		23.3% remission; 76.7% active	23.5% remission; 76.5% active	23.1% remission; 76.9% active	P = 0.999; χ2 = 0.977 (UC vs CD)
Age at onset (mean ± SD)		44.3 ± 14.55	48.82 ± 11.72	42.31 ± 17.93	P = 0.522 (UC vs CD)
Therapeutic regimen		23.3% drug free; 56.7% 5-ASA; 6.7% AZA; 13.3% biological treatment	29.4% drug free; 64.7% 5-ASA; 5.9% AZA	15.4% drug free; 46.2% 5-ASA; 7.7% AZA; 30.7% biological treatment	P = 0.096; χ2 = 6.336 (UC vs CD)
Extension (UC) and Location (CD)- Montreal			5.9% E1; 35.3% E2; 8.8% E3	15.4% L1; 23.1% L2; 61.5% L3
Behaviour- montreal				46.2% B1; 38.4% B2; 15.4% B3

IBD: Inflammatory bowel disease; UC: Ulcerative colitis; CD: Crohn’s disease; CTRL: Non-inflammatory bowel disease controls; M: Male; F: Female; 5-ASA: Aminosalicylates ; AZA: Azathioprine; E1: Proctitis; E2: Left-sided colitis; E3: Pancolitis; L1: Lerminal ileal; L2: Colon; L3: Leocolon; B1: Non-stricturing, non-penetrating; B2: Stricturing; B3: Penetrating.

Table 2 Gene expression levels in inflammatory bowel disease patients (mean ± SD)

Genes	2−∆Ct, CTRL (n = 17)	2−∆Ct, NIM (n = 30)	2−∆Ct, IM (n = 30)	1P value, case control (CTRL vs NIM)	1P value, case control (CTRL vs IM)	2P value, paired (IM vs NIM)
CNR1	0.014 ± 0.009	0.008 ± 0.005	0.018 ± 0.029	0.525	0.999	0.090
CNR2	0.010 ± 0.007	0.008 ± 0.006	0.025 ± 0.035	0.609	0.141	0.005
DAGLA	0.004 ± 0.003	0.005 ± 0.005	0.003 ± 0.003	0.924	0.999	0.153
DAGLB	0.006 ± 0.003	0.005 ± 0.003	0.005 ± 0.002	0.093	0.659	0.329
FAAH	0.032 ± 0.007	0.019 ± 0.014	0.012 ± 0.007	0.003	< 0.001	0.012
GPR18	0.013 ± 0.006	0.010 ± 0.005	0.014 ± 0.007	0.167	0.999	0.037
GPR55	0.008 ± 0.004	0.004 ± 0.002	0.008 ± 0.004	0.003	0.999	0.001
MGLL	0.107 ± 0.039	0.182 ± 0.266	0.127 ± 0.112	0.999	0.999	0.491
PPARG	0.088 ± 0.038	0.092 ± 0.055	0.045 ± 0.032	0.999	< 0.001	0.001
TRPV1	0.030 ± 0.015	0.023 ± 0.017	0.015 ± 0.010	0.248	0.002	0.032

¹Non-parametric one-way covariance analysis (ANCOVA) (Quade’s) followed by Bonferroni correction.

²Wilcoxon signed-rank test.

IBD: Inflammatory bowel disease; UC: Ulcerative colitis; CD: Crohn’s disease; CTRL: Non-inflammatory bowel disease controls; NIM: Noninflamed mucosa; IM: Inflamed mucosa; CNR2: Cannabinoid receptor 2; FAAH: Fatty acid amide hydrolase; GPR: G protein-coupled receptor 18; GPR55: G protein-coupled receptor 55; MGLL: Monoglyceride lipase; PPARG: Peroxisome proliferator-activated receptor gamma; TRPV1: Transient receptor potential cation channel, subfamily V, member 1; DAGLA: Diacylglycerol lipase alpha; DAGLAB: Diacylglycerol lipase beta.

Table 3 Gene expression levels in ulcerative colitis patients (mean ± SD)

Genes	2−∆Ct, CTRL (n = 17)	2−∆Ct, NIM (n = 17)	2−∆Ct, IM (n = 17)	1P value, case control (CTRL vs NIM)	1P value, case control (CTRL vs IM)	2P value, paired (IM vs NIM)
CNR1	0.014 ± 0.009	0.009 ± 0.006	0.014 ± 0.012	0.525	0.999	0.113
CNR2	0.010 ± 0.007	0.008 ± 0.007	0.021 ± 0.016	0.609	0.141	0.009
DAGLA	0.004 ± 0.003	0.005 ± 0.006	0.003 ± 0.003	0.924	0.999	0.113
DAGLB	0.006 ± 0.003	0.004 ± 0.002	0.005 ± 0.002	0.093	0.659	0.210
FAAH	0.032 ± 0.007	0.019 ± 0.011	0.012 ± 0.008	0.003	< 0.001	0.010
GPR18	0.013 ± 0.006	0.011 ± 0.006	0.014 ± 0.006	0.167	0.999	0.062
GPR55	0.008 ± 0.004	0.004 ± 0.002	0.007 ± 0.003	0.003	0.999	0.004
MGLL	0.107 ± 0.039	0.151 ± 0.127	0.089 ± 0.050	0.999	0.999	0.102
PPARG	0.088 ± 0.038	0.084 ± 0.045	0.047 ± 0.0035	0.999	< 0.001	0.019
TRPV1	0.030 ± 0.015	0.021 ± 0.011	0.014 ± 0.009	0.248	0.002	0.028

¹Non-parametric one-way covariance analysis (ANCOVA) (Quade’s) followed by Bonferroni correction.

²Wilcoxon signed-rank test.

IBD: Inflammatory bowel disease; UC: Ulcerative colitis; CD: Crohn’s disease; CTRL: Non-inflammatory bowel disease controls; NIM: Noninflamed mucosa; IM: Inflamed mucosa; CNR2: Cannabinoid receptor 2; FAAH: Fatty acid amide hydrolase; GPR: G protein-coupled receptor 18; GPR55: G protein-coupled receptor 55; MGLL: Monoglyceride lipase; PPARG: Peroxisome proliferator-activated receptor gamma; TRPV1: Transient receptor potential cation channel, subfamily V, member 1; DAGLA: Diacylglycerol lipase alpha; DAGLAB: Diacylglycerol lipase beta.

Table 4 Gene expression levels in Crohn’s disease patients

Genes	2−∆Ct, CTRL (n = 17)	2−∆Ct, NIM (n = 13)	2−∆Ct, IM (n = 13)	1P value, case control (CTRL vs NIM)	1P value, case control (CTRL vs IM)	2P value, paired (IM vs NIM)
CNR1	0.014 ± 0.009	0.007 ± 0.003	0.024 ± 0.043	0.113	0.457	0.552
CNR2	0.010 ± 0.007	0.007 ± 0.006	0.030 ± 0.052	0.213	0.432	0.173
DAGLA	0.004 ± 0.003	0.004 ± 0.004	0.004 ± 0.002	0.536	0.742	0.701
DAGLB	0.006 ± 0.003	0.005 ± 0.004	0.005 ± 0.003	0.079	0.229	0.861
FAAH	0.032 ± 0.007	0.020 ± 0.017	0.012 ± 0.007	0.003	<0.001	0.279
GPR18	0.013 ± 0.006	0.009 ± 0.004	0.014 ± 0.008	0.048	0.967	0.249
GPR55	0.008 ± 0.004	0.004 ± 0.003	0.008 ± 0.006	0.008	0.869	0.064
MGLL	0.107 ± 0.039	0.222 ± 0.390	0.175 ± 0.152	0.680	0.263	0.507
PPARG	0.088 ± 0.038	0.102 ± 0.069	0.041 ± 0.030	0.805	<0.001	0.023
TRPV1	0.030 ± 0.015	0.026 ± 0.023	0.017 ± 0.011	0.320	0.007	0.279

¹Mann-Whitney U test.

²Wilcoxon signed-rank test.

IBD: Inflammatory bowel disease; UC: Ulcerative colitis; CD: Crohn’s disease; CTRL: Non-inflammatory bowel disease controls; NIM: Noninflamed mucosa; IM: Inflamed mucosa; CNR2: Cannabinoid receptor 2; FAAH: Fatty acid amide hydrolase; GPR: G protein-coupled receptor 18; GPR55: G protein-coupled receptor 55; MGLL: Monoglyceride lipase; PPARG: Peroxisome proliferator-activated receptor gamma; TRPV1: Transient receptor potential cation channel, subfamily V, member 1; DAGLA: Diacylglycerol lipase alpha; DAGLAB: Diacylglycerol lipase beta.