Association of NOD1 (CARD4) insertion/deletion polymorphism with susceptibility to IBD: A meta-analysis

Table 1 Characteristics of the studies included in the meta-analysis

ID	Study	Yr	Ethnic group	Diseases	Sample size (frequency of GG allele, %)		OR (95%CI) for GG vs T allele	Hardy-Weinberg equilibrium of genotype control
					Case	Control
1	Hancock et al[19]	2008	Caucasian	CD	594 (27.1)	1024 (24.6)	1.130 (0.960-1.330)	0.010
2	Cantó et al[20]	2007	Caucasian	CD	97 (21.7)	50 (31.0)	0.615 (0.357-1.060)	0.147
3	Henckaerts et al[21]	2007	Caucasian	IBD	1052 (24.5)	280 (25.4)	0.952 (0.768-1.180)	0.751
				CD	809 (24.8)		0.973 (0.780-1.214)
				UC	222 (22.9)		0.878 (0.656-1.175)
4	Van Limbergen et al[22]	2007	Caucasian (Scottish)	IBD	1079 (26.1)	1233 (26.4)	0.984 (0.863-1.089)	0.261
				CD	515 (26.4)		1.003 (0.850-1.182)
				UC	537 (26.0)		0.985 (0.837-1.160)
5	Van Limbergen et al[22]	2007	Caucasian (Swedish)	IBD	632 (25.3)	277 (23.3)	1.112 (0.880-1.406)	0.741
				CD	244 (24.7)		1.086 (0.817-1.444)
				UC	388 (25.5)		1.129 (0.875-1.456)
6	Franke et al[23]	2006	Caucasian	IBD	961 (22.4)	841 (21.5)	1.055 (0.900-1.235)	0.958
				CD	633 (21.1)		0.983 (0.822-1.174)
				UC	332 (24.4)		1.181 (0.955-1.460)
7	Tremelling et al[24]	2006	Caucasian	IBD	1360 (25.2)	758 (25.7)	0.975 (0.844-1.126)	0.580
				CD	641 (24.9)		0.964 (0.812-1.144)
				UC	665 (25.4)		0.991 (0.837-1.173)
8	McGovern et al[25]	2005	Caucasian	IBD	664 (26.6)	335 (31.8)	0.777 (0.634-0.952)	0.195
				CD	358 (24.4)		0.694 (0.548-0.878)
				UC	306 (29.1)		0.880 (0.693-1.117)

OR: Odds ratio; IBD: Inflammatory bowel disease; CD: Crohn’s disease; UC: Ulcerative colitis.

Table 2 Meta-analysis of association between NOD1/CARD4 insertion/deletion polymorphism and inflammatory bowel disease

Polymorphism	Disease	Sample size		n	Test of association				Test of heterogeneity
		Case	Control		OR (95%CI)	Z	P value	Model	χ2	P value	I2(%)
GG vs T	Overall	12 878	9596	8	0.98 (0.90-1.07)	0.39	0.70	R	12.60	0.08	44.4
	CD	7782	9596	8	0.96 (0.86-1.07)	0.78	0.43	R	14.49	0.04	51.7
	UC	4900	7448	6	1.01 (0.92-1.09)	0.14	0.89	F	5.12	0.40	2.3
	IBD onset < 40	1486	4752	4	0.68 (0.50-0.93)	2.38	0.02	R	8.30	0.04	63.9
GG/T + GG/GG vs T/T	Overall	6439	4798	8	1.00 (0.98-1.08)	0.01	0.99	F	10.69	0.15	34.5
	CD	3891	4798	8	0.97 (0.86-1.10)	0.42	0.67	R	12.36	0.09	43.4
	UC	2450	3724	6	1.00 (0.90-1.11)	0.06	0.95	F	4.64	0.46	0.0
	IBD onset < 40	743	2376	4	0.71 (0.59-0.85)	3.65	0.0003	F	4.83	0.18	37.8
GG/GG vs T/T + GG/T	Overall	6439	4798	8	0.95 (0.81-1.11)	0.62	0.53	F	12.02	0.10	41.8
	CD	3891	4798	8	0.91 (0.76-1.09)	0.99	0.32	F	11.74	0.11	40.4
	UC	2450	3724	6	1.03 (0.83-1.27)	0.23	0.81	F	4.89	0.43	0.0
	IBD onset < 40	743	2376	4	0.61 (0.28-1.35)	1.22	0.22	R	7.98	0.05	62.3
GG/GG vs T/T	Overall	4033	3020	8	0.93 (0.74-1.17)	0.63	0.53	R	12.59	0.08	44.4
	CD	2442	3020	8	0.88 (0.68-1.14)	0.96	0.34	R	12.96	0.07	46.0
	UC	1623	2312	6	0.97 (0.78-1.20)	0.32	0.75	F	3.04	0.69	0.0
	IBD onset < 40	500	1435	4	0.52 (0.22-1.21)	1.52	0.13	R	8.84	0.03	66.0
GG/T vs T/T	Overall	2816	2098	8	0.95 (0.80-1.12)	0.64	0.53	F	10.85	0.15	35.5
	CD	1685	2098	8	0.92 (0.76-1.11)	0.92	0.36	F	9.94	0.19	29.6
	UC	1093	1648	6	1.03 (0.83-1.28)	0.27	0.79	F	4.67	0.46	0.0
	IBD onset < 40	290	1112	4	0.94 (0.64-1.37)	0.33	0.74	F	5.95	0.11	49.6

R: Random effect model; F: Fixed effect model; IBD: Inflammatory bowel disease; CD: Crohn’s disease; UC: Ulcerative colitis.

Table 3 Egger’s linear regression test to measure the funnel plot asymmetry¹

Comparisons	Y axle intercept: a (95%CI)
	GG vs T	GG/T + GG/GG vs T/T	GG/GG vs T/T + GG/T	GG/GG vs T/T	GG/T vs T/T
Overall	-1.92 (-5.57-1.72)	0.96 (-2.65-4.58)	2.38 (-0.87-5.64)	2.38 (-1.00-5.77)	2.32 (-0.71-5.36)
CD	-2.62 (-6.54-1.29)	1.60 (-2.38-5.59)	2.79 (-0.20-5.78)	2.89 (-0.31-6.09)	2.51 (-0.29-5.33)
UC	-0.39 (-6.54-5.75)	0.57 (-5.25-6.39)	-0.57 (-7.13-5.97)	-0.43 (-7.00-6.13)	-0.57 (-6.89-5.74)
IBD onset at < 40 yr of age	-2.16 (-8.80-4.47)	1.49 (-4.16-7.15)	1.86 (-4.04-7.77)	1.94 (-4.40-8.29)	1.63 (-3.48-6.75)

¹All P > 0.05. IBD: Inflammatory bowel disease; CD: Crohn’s disease; UC: Ulcerative colitis.