NOD2/CARD15 gene mutations in North Algerian patients with inflammatory bowel disease

Table 1 Demographic, clinical data and genotype-phenotype correlations in Crohn's disease patients n (%)

Variables	All subjects	Non carriers	Carriers	P value
HC	114	102 (89.47)	12 (10.52)	0.120
CD patients	86	70 (81.39)	16 (18.6)	0.103
Sex (F/M)	46/40	40/30	6/10	0.155
Age at diagnosis	25.28± 14.85	25.70 ± 15.55	22.12 ± 10.66
A1	28 (32.5)	22	6	0.809
A2	43 (50)	35	8
A3	15 (17.5)	13	2
Location
L1: Ileum	25 (29)	23	2	0.020
L2: Ileo-colon	49 (57)	35	14
L3: Colon	12 (14)	12	0
Resective Surgery	37 (43)	31	6	0.620
EIM	24 (28)	18	6	0.343
Positive family history for CD	23 (27)	17	6	0.281

A1 < 16, A2 = 16-40, A3 > 40 years according Montreal classification. CD: Crohn's disease; HC: Healthy controls; EIM: Extra intestinal manifestations.

Table 2 Demographic, clinical data and genotype-phenotype correlations in ulcerative colitis patients n (%)

Variables	All subjects	Non carriers	Carriers	P value
HC	114	102 (89.47)	12 (10.52)	0.120
UC patients	46	42(91.3)	4(8.7)	0.726
Sex (F/M)	30/16	27/15	3/1	0.667
Age at diagnosis	36.86 ± 12.30	36.92 ± 11.34	36.25 ± 22.60
A1	1 (2.1)	1	0	0.916
A2	31 (67.4)	28	3
A3	14 (30.5)	13	1
Location
E1: proctitis	9 (20)	9	0	0.115
E2: distal colitis	19 (41.5)	16	3
E3: extensive colitis	18 (39)	17	1
Resection Surgery	4 (9)	3	1	0.225
EIM	11 (24)	11	0	0.240
Positive family history for UC	11 (24)	10	1	0.957

A1 < 16, A2 = 16-40, A3 40 years according Montreal classification. UC: Ulcerative colitis; HC: Healthy controls; EIM: Extra intestinal manifestations.

Table 3 NOD2 Allele frequencies in Crohn's disease, ulcerative colitis and healthy control groups

Polymorphisms		Allele frequency (%)
		CD	UC	HC	IBD	P value1	OR	P value2	OR	P value3	OR	P value4	OR
		(n = 86)	(n = 46)	(n = 114)	(n = 132)		(95%CI)		(95%CI)		(95%CI)		(95%CI)
p.Arg702Trp (C/T)	C	92	98	95	94	0.09	3.67	0.40	1.47	1.00	0.92	0.36	2.5
	T	8	2	5	6		0.48-4.87		0.65-3.31		0.42-2.01		0.54-11.4
p.Gly908Arg (G/C)	G	97	99	98	98	0.66	2.72	0.50	1.67	0.75	0.76	1.00	1.62
	C	3	1	2	2		0.31-23.69		0.44-6.34		0.21-2.75		0.17-14.74
p.Leu1007fsinsC (WT/insC)	WT	98	98	99	98	1.00	1.07	0.40	2.69	0.29	0.38	0.32	0.39
	insC	2	2	1	2		0.19-5.9		0.48-14.87		0.07-1.9		0.05-2.87
Total frequency (%)		13	5	8	10	0.08	0.39	0.12	1.71	0.43	1.32	0.63	0.67
							0.14-1.07		0.88-3.3		0.71- 2.48		0.24-1.86

¹The P value for CD patients vs UC patients;

²The P value for CD patients vs HC group;

³The P value for IBD patients vs HC group;

⁴The P value for UC patients vs HC group. (%) represents allele frequency. CD: Crohn's disease; UC: Ulcerative colitis; IBD: İnflammatory bowel disease (CD + UC patients); HC: Healthy controls; WT: Wild type allele; insC: Insertion mutation of a C.

Table 4 Number of different genotypes observed in Crohn's disease/ulcerative colitis/healthy controls groups

Variant	p.Arg702Trp	p.Gly908Arg	p.Leu1007fsinsC	WT
p.Arg702Trp	2/0/4	1/0/1	2/1/1	6/1/2
p.Gly908Arg		0/0/0	1/0/0	3/1/3
p.Leu1007fsinsC			0/0/0	1/1/1
WT				70/42/102

In each cell of the table, the genotype is obtained by combining the two genetic variants indicated in the corresponding row and column. No patients homozygous for NOD2 gene p.Gly908Arg and p.Leu1007fsinsC mutations were found in this study. CD: Crohn's disease; UC: Ulcerative colitis; HC: Healthy controls; WT: Wild type.

Table 5 Hardy-Weinberg equilibrium and the P value

		NOD2 polymorphisms
		p.Arg702Trp				p.Gly908Arg				p.Leu1007fsinsC
Groups	Genotypes	CC	CT	TT	P value	GG	GC	CC	P value	WT/WT	insC/WT	insC/insC	P value
	Frequencies
HC	Observed	92.98	3.51	3.51	0	96.49	3.51	0	0.8488	98.25	1.75	0	0.9247
	Expected	89.75	9.97	0.28		96.52	3.45	0.03	NS	98.25	1.74	0	NS
CD	Observed	87.21	10.46	2.33	0.0117	94.19	5.81	0	0.7813	95.35	4.65	0	0.8252
	Expected	86.92	12.62	0.46		94.27	5.64	0.08	NS	95.41	4.54	0.05	NS
IBD	Observed	90.15	8.33	1.52	0.0106	95.45	4.55	0	0.7893	95.45	4.55	0	0.7893
	Expected	88.96	10.72	0.32		95.51	4.44	0.05	NS	95.51	4.44	0.05	NS

CD: Crohn's disease; HC: Healthy controls; IBD: İnflammatory bowel disease; NS: Non-significant P value; WT: Wild type; insC: Insertion mutation of a C.

Table 6 Comparative study of NOD2 allele frequencies in North African populations

Population	Number		Allele frequency (%)
			p.Arg702Trp		p.Gly908Arg		p.Leu1007fsinsC		Total allele
	CD	HC	CD	HC	CD	HC	CD	HC	CD	HC
North Algeria (this study)	86	114	8	5	3	2	2	1	13	8
Algeria[25]	204	201	5	0.50	3	0.5	ND	ND	ND	ND
Morocco[23]	101	107	0.49	0.46	6.43	2.8	0.9	0	8	3.2
Tunisia[24]	130	90	2	0.60	5	3	1	0	8	3.6

CD: Crohn's disease; HC: Healthy controls; ND: Not determined.