Single-nucleotide polymorphisms of matrix metalloproteinases and their inhibitors in gastrointestinal cancer

Table 1 Effects of matrix metalloproteinases single nucleotide polymorphisms on promoter activity

MMP	SNP	Effect of mutation	Influence on promoter activity in vitro	Reference
MMP-1	-1607 1G/2G	Extra Guanine (2G) creates a binding site for transcription factor Ets-1	Increased in 2G allele (4-fold)	Rutter et al[18]
MMP-2	-1306 C/T	C to T substitution disrupts Sp-1 binding site	Decreased in T-allele	Price et al[22]
MMP-2	-735 C/T	C to T substitution influences Sp-1 binding site	Decreased in T-allele	Yu et al[15]
MMP-2	-790 T/G	Three transcription factors1 bind to T (but not G) allele sequence	Decreased in G allele2	Vasku et al[28]
MMP-2	-955 A/C	Unknown	Effect unclear	Price et al[22]
MMP-2	-1575 G/A	G to T substitution decreases estrogen receptor α binding	Decreased in A allele	Harendza et al[27]
MMP-3	-1171 5A/6A3	Transcription suppressor binds with higher affinity to 6A allele	Decreased in 6A allele (2-fold)	Ye et al[19]
MMP-3	Lys45Glu	Lys to Glu substitution in exon 2 of gene	Effect unclear	Ouyang et al[16]
MMP-7	-181 A/G	Nuclear proteins bind with higher affinity to G allele	Increased in G allele4 (2- to 3- fold)	Jormsjö et al[17]
MMP-7	-153 C/T	T allele binds additional nuclear proteins compared with C allele	Increased in T allele4 (2- to 3- fold)	Jormsjö et al[17]
		affinity for proteins that bind to both alleles higher in C allele
MMP-8	-799 C/T	Influences binding of transcription factor?	Increased in T allele5	Wang et al[23]
MMP-8	17 C/G	Influences binding of transcription factor?	Increased in G allele5	Wang et al[23]
MMP-9	-90 CA(n)	Number of repeats influences strength of nuclear binding	Increased in n = 21 vs n = 14, n = 18	Shimajiri et al[12]
MMP-9	-1562 C/T	C to T substitution disrupts nuclear protein binding site	Increased in T allele	Zhang et al[20]
MMP-9	R279Q	Arg to Gln substitution in fibronectin type II domains	Effect unclear6	Wu et al[13]
MMP-9	P574R	Pro to Arg substitution in hemopexin domain	Effect unclear6	Wu et al[13]
MMP-9	R668Q	Arg to Gln substitution in hemopexin domain	Effect unclear6	Wu et al[13]
MMP-12	-82 A/G	A to G substitution results in decreased affinity for transcription factor AP-1	Decreased in G allele	Jormsjö et al[21]
MMP-12	1082 A/G	Asn to Ser substitution at coding region of hemopexin domain	Effect unclear	Joos et al[25]
MMP-13	-77 A/G	A to G substitution results in decreased affinity for transcription factor AP-1	Decreased in G allele (2-fold)	Yoon et al[24]
MMP-21	C572T	Ala to Val substitution in enzymes catalytic domain	Effect unclear	Shagisultanova et al[29]
TIMP-1	372 C/T	Unknown, located in exon 5, no effect on transcription or amino-acid sequence	Effect unclear	Hinterseher et al[26]
TIMP-2	-418 G/C	G to C substitution results in disruption of Sp-1 binding site	Decreased in C allele2	Hirano et al[30]
TIMP-2	303C/T	Unknown, located in exon 3, no effect on transcription or amino-acid sequence	Effect unclear	Kubben et al[14]

¹The three transcription factors are: GKLF (Gut-enriched Krueppel-like factor), S8 and Evi1 (ectopic viral integration site 1 encoded factor);

²Not confirmed;

³Formerly known as -1612 5A/6A;

⁴Only in combination MMP-7 -181G/-153T;

⁵Only in combination MMP-8 -799T/-381G/+17G, in cells resembling chorion cytotrophoblasts;

⁶Probably influences substrate binding and inhibitor binding. MMP: Matrix metalloproteinase; SNP: Single-nucleotide polymorphisms; TIMP: Tissue inhibitor of metalloproteinase.