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

doi:10.3748/wjg.v11.i27.4188

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World Journal of Gastroenterology

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1007-9327

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Baishideng Publishing Group Inc, 7041 Koll Center Parkway, Suite 160, Pleasanton, CA 94566, USA

Clinical Research

World J Gastroenterol. Jul 21, 2005; 11(27): 4188-4193
Published online Jul 21, 2005. doi: 10.3748/wjg.v11.i27.4188

Table 1 Clinical characteristics of study subjects

Characteristics	Patients with		Controls
Characteristics	UC	CD	Controls
Number of subjects	108	79	200
Age range (yr)	14 - 83	17 - 75	20 - 60
Age (mean±SD)	44.0 ± 16.9^b	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
Polymorphic site	Allele	UC	CD	Controls
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)
Polymorphic site	Genotype	UC (n = 108)	CD (n = 79)	Controls (n = 200)
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)
Polymorphic site		Genotype	(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)
Polymorphic site			Genotype		(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).

Citation: Machida H, Tsukamoto K, Wen CY, Narumi Y, Shikuwa S, Isomoto H, Takeshima F, Mizuta Y, Niikawa N, Murata I, Kohno S. Association of polymorphic alleles of CTLA4 with inflammatory bowel disease in the Japanese. World J Gastroenterol 2005; 11(27): 4188-4193
URL: https://www.wjgnet.com/1007-9327/full/v11/i27/4188.htm
DOI: https://dx.doi.org/10.3748/wjg.v11.i27.4188