Association of polymorphic alleles of CTLA4 with inflammatory bowel disease in the Japanese

Table 1 Clinical characteristics of study subjects

Characteristics	Patients with		Controls
	UC	CD
Number of subjects	108	79	200
Age range (yr)	14 - 83	17 - 75	20 - 60
Age (mean±SD)	44.0 ± 16.9b	34.5 ± 12.7	32.5 ± 11.1
Male/female (%)	57 (52.8)/51 (47.2) 47 (59.5)/32 (40.5) 125 (62.5)/75 (37.5)

^bP<0.01 vs controls.

Table 2 Distribution of CTLA4 polymorphic alleles among study subjects

Polymorphic site	Allele	Number (%) of alleles in		Controls
		UC	CD
nt –318	C	192 (88.9)	140 (88.6)	362 (90.5)
	T	24 (11.1)	18 (11.4)	38 (9.5)
nt +49	A	84 (38.9)	59 (37.3)	159 (39.8)
	G	132 (61.1)	99 (62.7)	241 (60.2)
nt +6 230	G	158 (73.1)	115 (72.8)	278 (69.5)
	A	58 (26.9)	43 (27.2)	122 (30.5)
(AT)n in 3’-UTR	(AT)7	107 (49.5)	83 (52.5)	205 (51.3)
	(AT)15	45 (20.8)	22 (13.9)	82 (20.5)
	(AT)16	50 (23.1)	35 (22.2)	87 (21.8)
	(AT)17	3 (1.4)	15 (9.5)	16 (4.0)
	(AT)18	11 (5.1)	1 (0.6)	8 (2.0)
	(AT)20	0	2 (1.3)	0
	(AT)22	0	0	2 (0.5)
Total number of alleles		216	158	400

Table 3 Distribution of CTLA4 genotypes among study subjects

Polymorphic site	Genotype	Number (%) of subjects with genotype		Controls (n = 200)
		UC (n = 108)	CD (n = 79)
nt –318	C/C	84 (77.8)	63 (79.8)	163 (81.5)
	C/T	24 (22.2)	14 (17.7)	36 (18.0)
	T/T	0	2 (2.5)	1 (0.5)
nt +49	A/A	14 (13)	9 (11.4)	33 (16.5)
	A/G	56 (51.8)	41 (51.9)	93 (46.5)
	G/G	38 (35.2)	29 (36.7)	74 (37.0)
nt +6 230	G/G	54 (50)	39 (49.4)	100 (50.0)
	G/A	50 (46.3)	37 (46.8)	78 (39.0)
	A/A	4 (3.7)	3 (3.8)	22 (11.0)
(AT)n in 3’-UTR	(AT)7/(AT)7	52 (48.1)	41 (51.9)	101 (50.5)
	(AT)7/(AT)15	2 (1.9)	1 (1.3)	1 (0.5)
	(AT)7/(AT)16	1 (0.9)	0	2 (1.0)
	(AT)15/(AT)15	16 (14.8	5 (6.3)	31 (15.5)
	(AT)15/(AT)16	11 (10.2)	9 (11.4)	18 (9.0)
	(AT)15/(AT)17	0	2 (2.5)	1 (0.5)
	(AT)16/(AT)16	18 (16.7)	13 (16.4)	30 (15.0)
	(AT)16/(AT)17	2 (1.9)	0	6 (3.0)
	(AT)16/(AT)18	0	0	1 (0.5)
	(AT)17/(AT)17	0	6 (7.6)	3 (1.5)
	(AT)17/(AT)18	1 (0.9)	1 (1.3)	3 (1.5)
	(AT)18/(AT)18	5 (4.6)	0	2 (1.0)
	(AT)20/(AT)20	0	1 (1.3)	0
	(AT)22/(AT)22	0	0	1 (0.5)

Table 4 Number of subjects with or without “G” allele at the G+6230A SNP site of CTLA4

Genotype	Number (%) of subjects with genotype
	UC	CD	Control
	(n = 108)	(n = 79)	(n = 200)
G/G+G/A	104 (96.3)	76 (96.2)	178 (89)
A/A	4 (3.7)a	3 (3.8)	22 (11)

^aP<0.05 vs controls (P = 0.047, OR = 0.311).

Table 5 Number of UC patients classified by clinical features

Polymorphic site		Genotype	Number of patients	Age at onset (yr)
			(n = 108, %)	<40	≥40
C–318T		C/C	84 (77.8)	55	29
		C/T	24 (22.2)	18	6
		T/T	0	0	0
A+49G		A/A	14 (13.0)	8	6
		A/G	56 (51.8)	40	16
		G/G	38 (35.2)	25	13
G+6230A		G/G	54 (50.0)	39	15
		G/A	50 (46.3)	31	19
		A/A	4 (3.7)	3	1
(AT)n in 3’-UTR		(AT)7/(AT)7	52 (48.1)	33	19
		(AT)7/(AT)x or others	56 (51.9)	40	16
(Continued)
Location			Colectomy
Pancolitis	Left-sided colitis	Proctitis	Yes		No
42	29	13	7		77
10	13	1	1		23
0	0	0	0		0
9	4	1	0		14`
28	20	8	3		53
15	18	5	5		33
20	27	7	6		48
28	15	7	2		48
4	0	0	0		4
31	14	7	1		51
23	26	7	7		49

Table 6 Number of CD patients classified by clinical features

Polymorphic site			Genotype		Number of patients	Age at onset (yr)
					(n = 79, %)	<40	≥40
C–318T			C/C		63 (79.8)	54	9
			C/T		14 (17.7)	12	2
			T/T		2 (2.5)	2	0
A+49G			A/A		9 (11.4)	8	1
			A/G		41 (51.9)	35	6
			G/G		29 (36.7)	25	4
G+6230A			G/G		39 (49.4)	35	4
			G/A		37 (46.8)	30	7
			A/A		3 (3.8)	3	0
(AT)n in 3'-UTR			(AT)7/(AT)7		41 (51.9)	34	7
			(AT)7/(AT)x or others		38 (48.1)	34	4
(Continued)
Location of lesion			Operation		Fistula
Ileocolon	Ileum	Colon	Yes	No	Presence		Absence
40	14	9	33	30	27		36
11	1	2	9	5	8		6
2	0	0	2	0	2		0
7	2	0	5	4	5		4
25	11	5	20	21	14		27
21	2	6	19	10	18		11
25	5	7	21	18	19		20
25	8	4	22	15	18		19
1	2	0	1	2	0		3
27	10	4	24	17	19		22
26	9	3	20	18	17		21

Table 7 Relationship between genotype at the A+49G SNP site and presence/absence of fistula in CD patients

Genotype	No. (%) of patients
	With fistula	Without fistula
	(n = 37)	(n = 42)
A/A+A/G	19 (51.4)	31 (73.8)
G/G	18 (48.6)a	11 (26.2)

^aP<0.05 vs without fistula (P = 0.0388, OR = 2.67).