Polymorphisms in interleukin-10 gene according to mutations of NOD2/CARD15 gene and relation to phenotype in Spanish patients with Crohn’s disease

Table 1 Distribution of IL-10G14 microsatellite allele and -1082G allele stratified by NOD2/CARD15 status

Allele frequencies	At least one CARD15/NOD2 mutation positiven = 76 (%)	CARD15/NOD2 mutation negativen = 129 (%)	P
IL-10G14 (n = 47)	22 (28.9)	25 (19.4)	0.115
-1082G (n = 146)	54 (71.1)	92 (71.3)	0.96
IL-10G14+-1082G (n = 29)	13 (17.1)	16 (12.4)	0.35

Table 2 Distribution of -1082G allele among different clinical subgroups of CD stratified by NOD2/CARD15 status

Phenotypic characteristics	Phenotype frequency of -1082 IL-10G(+)(n = 146) (%)	P	CARD15/NOD2 (+) -1082 IL-10 G(+)(n = 54) (%)	P	CARD15/NOD2 (-) -1082 IL-10 G(+)(n = 92) (%)	P
Sex
Men	67 (45.9)	0.67	24 (44.4)	0.77	43 (46.7)	0.45
Women	79 (54.1)		30 (55.5)		49 (53.3)
Age at diagnosis (yr)
A1, < 40	117 (80.1)		46 (85.2)	0.5	71 (77.2)	0.41
A2, ≥40	29 (19.9)	0.72	8 (14.8)		21 (22.8)
Family history	27 (18.5)	0.43	10 (18.5)	0.43	17 (18.5)	0.76
Smokers	64 (43.8)	0.55	24 (44.4)	0.86	40 (43.5)	0.65
Appendectomy	20 (13.7)	0.55	7 (12.9)	0.93	13 (14.1)	0.49
Tonsillectomy	22 (15.1)	0.11	5 (9.3)	0.66	17 (18.5)	0.19
Disease behavior
Nonstricturing, nonpenetrating (B1)	63 (43.2)	0.87	24 (44.4)	0.58	39 (42.4)	0.86
Stricturing (B2)	22 (15.1)		9 (16.7)		13 (14.1)
Penetrating (B3)	61 (41.8)		21 (38.9)		40 (43.5)
Location of disease
Terminal ileum (L1)	70 (47.9)	0.63	29 (53.7)	0.021	41 (44.6)	0.43
Colon (L2)	24 (16.4)		5 (9.3)		19 (20.7)
Ileocolon (L3)	47 (32.2)		19 (35.2)		28 (30.4)
Upper gastrointestinal (L4)	5 (3.4)		1 (1.9)		4 (4.3)
Perianal	39 (26.7)	0.3	11 (20.4)	1	28 (30.4)	0.3
Extraintestinal clinical manifestations
Cutaneous	27 (18.5)	0.56	9 (16.7)	0.29	18 (19.6)	0.93
Articular	49 (33.6)	0.69	16 (29.6)	0.83	33 (35.9)	0.83
Treatment
Surgical intervention	61 (41.8)	0.76	22 (40.7)	0.71	39 (42.4)	0.92
Infliximab	19 (13.0)	0.06	5 (9.3)	0.032	14 (15.2)	0.61
Immunosuppressants	63 (43.2)	0.81	25 (46.3)	0.72	38 (41.3)	0.63

¹ -1082G allele in NOD2/CARD15 mutation positive patients: ileocolonic location (P = 0.008, RR = 1.52, 95% CI = 1.21-1.91). ² -1082G allele in NOD2/CARD15 mutation positive patients: infliximab (P = 0.03, RR = 0.54, 95%CI = 0.27-1)

Table 3 Distribution of IL-10G14 allele among the different clinical subgroups of CD stratified by NOD2/CARD15 status

Phenotypic characteristics	Phenotypefrequencyof IL-10.G14 (+)(n=47) (%)	P	CARD15/NOD2 (+) IL-10.G14,(n = 22) (%)	P	CARD15/NOD2 (-)IL-10.G14,(n = 25) (%)	P
Sex
Men	23 (48.9)	0.74	13 (59.1)	0.08	10 (40)	0.32
Women	24 (51.1)		9 (40.9)		15 (60)
Age at diagnosis (yr)
A1, < 40	39 (83.0)	0.5	21 (95.5)	0.27	18 (72)	0.68
A2, ≥40	8 (17.0)		1 (4.5)		7 (28)
Family history	9 (19.1)	0.54	4 (18.2)	0.52	5 (20)	0.88
Smokers	24 (51.1)	0.51	16 (72.7)	0.021	8 (32)	0.41
Appendectomy	9 (19.1)	0.32	6 (27.3)	0.0022	3 (12)	0.59
Tonsillectomy	5 (10.6)	0.63	3 (13.6)	0.48	2 (8)	0.36
Disease behavior
Nonstricturing, nonpenetrating (B1)	19 (40.4)	0.61	6 (27.3)	0.19	13 (52)	0.62
Stricturing (B2)	9 (19.1)		6 (27.3)		3 (12)
Penetrating (B3)	19 (40.4)		10 (45.5)		9 (36)
Location of disease
Terminal ileum (L1)	23 (48.9)	0.26	15 (68.2)	0.54	8 (32)	0.24
Colon (L2)	4 (8.5)		1 (4.5)		3 (12)
Ileocolon (L3)	17 (36.2)		5 (22.7)		12 (48)
Upper gastrointestinal (L4)	3 (6.4)		1 (4.5)		2 (8)
Perianal	14 (29.8)	0.86	4 (18.2)	0.47	10 (40)	0.28
Extraintestinal clinical manifestations
Cutaneous	8 (17.0)	0.62	3 (13.6)	0.3	5 (20)	0.56
Articular	13 (27.7)	0.32	6 (27.3)	0.53	7 (28)	0.36
Treatment
Surgical intervention	20 (42.6)	0.98	10 (45.5)	0.8	10 (40)	0.82
Infliximab	7 (14.9)	0.79	5 (22.7)	0.31	2 (8)	0.21
Immunosuppressants	18 (38.3)	0.61	10 (45.5)	0.81	8 (32)	0.23

¹IL-10G14 in NOD2/CARD2 mutation positive patients: smokers vs non-smokers (P = 0.02, RR = 2.47, 95%CI = 1.28-4.8).

²IL-10 G14 in NOD2/CARD2 mutation positive patients: appendectomy vs non-appendectomy (P = 0.002, RR = 3.29, 95%CI = 1.45-7)