Role of matrix metalloproteinase, tissue inhibitor of metalloproteinase and tumor necrosis factor-α single nucleotide gene polymorphisms in inflammatory bowel disease

Table 1 Genotype distributions at SNP loci in IBD patients compared to controls

Protein	SNP	Genotype	IBD(% of patients)	Controls(% of individuals)	Allele	IBD(% of total)	Controls(% of total)
MMP-1	-1607 1G/2G	1G1G	31	26.6	1G	55.4	51.4
	11q22-q23	1G2G	49	49.6	2G	44.6	48.6
		2G2G	20.1	23.8
MMP-2	-1306 C/T	CC	57.7	61.9	C	75.5	76.8
	16q13	CT	35.6	29.9	T	24.5	23.2
		TT	6.7	8.2
MMP-3	-1613 5T/6T	5T5T	29.2	27.9	5T	52.3	52
	11q23	5T6T	46.3	48.4	6T	47.7	48
		6T6T	24.6	23.8
MMP-9	-1562 C/T	CC	72.4	69.7	C	85.6	84
	20q11.2-q13.1	CT + TT	27.6	30.3	T	14.4	16
♂, TIMP-11	+372 T/C	T	61.6	51.6	T	61.6	51.6
	Xp11.3-p11.23	C	38.4	48.4	C	38.4	48.4
♀, TIMP-11	+372 T/C	TT	31.2	23.8	T	52.8	50.7
	Xp11.3-p11.23	TC	43.3	53.6	C	47.2	49.3
		CC	25.5	22.5
TIMP-2	+303 G/A	GG	77.5	78.7	G	88.3	89.1
	17q25	GA + AA	22.5	21.3	A	11.7	10.9
TNF-α	-308 G/A	GG	68.8	69.7	G	82.0	83.0
	6p21	GA + AA	31.4	30.3	A	18.0	17.0

n = 239-240/245 IBD patients vs n = 244/248 controls with successful genotype determinations.

¹For TIMP-1, ♂ these numbers are 99/101 vs 93/96 and for TIMP-1, ♀ 141/144 vs 151/152. Note: for MMP-9, TNF-α and TIMP-2 frequency of the homozygote mutant genotype (TT, AA and AA, respectively), was below 5% and these groups were combined with the corresponding heterozygote group, solely for the purpose of accurate statistical analysis. No statistically significant differences (Chi-Square testing) in genotype distributions or allele frequencies were found between IBD and controls.

Table 2 TIMP-1 genotype distribution at SNP + 372 C/T in CD patients compared to controls

Protein	Genotype	CD (% of patients)	Controls (% of individuals)	P1	Allele	CD (% of total)	Controls (% of total)	P-value
TIMP-1, ♂	T	67.9	51.6	0.055	T	67.9	51.6	0.055
	C	32.1	48.4		C	32.1	48.4
TIMP-1, ♀	TT	39	23.8	0.018	T	56.5	50.7	0.238
	TC	35.1	53.6		C	43.5	49.3
	CC	26	22.5

♂: n = 53/54 vs 93/96; ♀: n = 77/80 vs 151/152 successful genotype determinations, respectively. ¹P-value, Chi-Square test.

Table 3 Effect of MMP, TIMP and TNF-α allelic SNP composition on age at onset of disease, colon involvement at first endoscopic/radiologic examination and development of fistulae or stenotic strictures during follow-up [median 24.7 (range 3.3-58.5) yr] in CD

Protein	SNP	Genotype	Number ofpatients	Age (yr) at onsetof disease,median (range)	Colonic involvementat first examination(% of patients)	Fistulae duringfollow-up(% of patients)	Strictures duringfollow-up(% of patients)
MMP-1	-1607 1G/2G	1G1G	38	20.7 (0.3-45.6)	52.6	71.1	84.2
		1G2G	54	22.4 (7.0-61.5)	50	63	75.9
		2G2G	26-27	21.0 (3.4-40.2)	57.7	63	70.4
MMP-2	-1306 C/T	CC	66-67	20.1 (5.8-61.5)	57.6	64.2	74.6
		CT+TT	521	22.4 (0.3-50.1)	46.2	67.3	80.8
MMP-3	-1613 5T/6T	5T5T	34	22.4 (0.3-53.6)	35.3a	70.6	91.2a
		5T6T	54	19.3 (3.4-61.5)	63	66.7	74.1
		6T6T	30-31	23.5 (7.2-49.1)	53.3	58.1	67.7
MMP-9	-1562 C/T	CC	88-89	21.0 (0.3-61.5)	53.4	68.5	75.3
		CT+TT	301	22.7 (7.2-45.5)	50	56.7	83.3
TIMP-1, ♂	+372 T/C	T	32	18.9 (0.3-48.3)	53.1	78.1	87.5
		C	17	18.5 (5.9-61.5)	52.9	76.5	94.1
TIMP-1, ♀	+372 T/C	TT	29	24.3 (7.0-56.8)	55.2	41.4c	69.0
		TC	22-23	23.5 (3.4-39.6)	45.5	69.6	78.3
		CC	18	22.2 (10.4-49.1)	55.6	66.7	55.6
TIMP-2	+303 G/A	GG	91-92	21.5 (0.3-61.5)	56.0	68.5	77.2
		GA+AA	271	22.4 (3.4-56.8)	40.7	55.6	77.8
TNF-α	-308 G/A	GG	79-80	22.6 (0.3-61.5)	50.6	68.8	78.8
		GA+AA	391	18.9 (3.4-45.5)	56.4	59.0	74.4

¹Only 7, 1, 2 and 4 patients were carrying the MMP-2, -9, TIMP-2 or TNF-α mutant genotype, respectively, and were combined with the heterozygote group for statistical purposes. Differences in phenotype between genotypes were tested for statistical significance by Kruskal-Wallis/Mann-Whitney U (onset) or Chi-Square test (colon involvement/fistulae and stricture development).

^aP≤ 0.03 vs 5T6T and 6T6T combined,

^cP = 0.025 vs TC and CC combined.