Association of MMP-9 gene polymorphisms with acute coronary syndrome in the Uygur population of China

Abstract

Abstract:

BACKGROUND: Matrix metalloproteinase-9 (MMP-9) plays a pivotal role in early atherosclerosis, vascular remodeling and development of atherosclerotic lesion. The potentially functional MMP-9 gene polymorphism may contribute to the susceptibility of acute coronary syndrome (ACS). This study aimed to investigate the association between two single nucleotide polymorphisms (-1562C>T, R279Q) of the MMP-9 gene in patients with ACS in the Uygur population of China.
METHODS: This case-control study was composed of 361 ACS patients and 432 control subjects, who had undergone coronary angiography. Among the ACS patients, 162 (44.9%) had single-vessel disease, 145 (40.2%) had two-vessel disease, and 54 (14.9%) had three-vessel disease. The genotypes of the two selected SNPs were determined by the method of polymerase chain reaction and restriction fragment length polymorphism (RFLP-PCR). The relationship between the polymorphism of the MMP-9 gene and the severity of coronary arterial stenosis was analyzed.
RESULTS: Analysis of the two SNPs showed that the frequency of CT and TT genotypes in patients with ACS was significantly higher than that in the control group (ACS vs. controls; CT+TT: 25.5% vs. 15.8%, P=0.001). And the -1562 gene allele (C/T) was significantly associated with acute coronary syndrome (ACS vs. controls; C allele: 85.7% vs. 91.5%, T allele: 14.3% vs. 8.5%, P<0.001). But the frequencies of CT+TT and CC genotypes were not statistically different among ACS patients with one, two and three or more significantly diseased vessels (P=0.55). The R279Q polymorphism site with regard to the association with ACS was not significant (P>0.05). The presence of CT or TT genotypes, assuming codominant effect of the T allele, was independently associated with increased risk of coronary artery disease when adjustment was made for age, body mass index, smoking, hypertension and diabetes mellitus [odds ratio=1.737 (95% confidence interval, 1.337-2.257), P=0.018].
CONCLUSIONS: MMP-9-1562C>T polymorphism is associated with the susceptibility to ACS in the Uygur population of China. However, this mutation apparently is not related to the severity of coronary arterial stenosis. Another SNP (R279Q) polymorphism of MMP-9 is not significantly associated with the risk of ACS.

Key words: Matrix metalloproteinase-9, Acute coronary syndrome, Uygur, Gene polymorphism

Lei Wang, Yi-tong Ma, Xiang Xie, Yi-ning Yang, Zhen-yan Fu, Fen Liu, Xiao-mei Li, Bang-dang Chen. Association of MMP-9 gene polymorphisms with acute coronary syndrome in the Uygur population of China[J]. World Journal of Emergency Medicine, 2011, 2(2): 104-110.

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Polymorphism (dbSNP No.)	Primer sequence (sense/antisense)	Initial denature	Denature	Annealing	Extension	Cycles	Final incubation
-1562C>T	F:5'-GCCTGGCACATAGTAGGCCC-3'	95 °C	94 °C	64.5 °C	72 °C	35	72 °C
(rs3918242)	R:5'-CTTCCTAGCCAGCCGGCATC-3'	5 min	30 s	30 s	45 s		10 min
R279Q	F:5'-ATGGGTCAAAGAACAGGA-3'	95 °C	94 °C	58 °C	72 °C	30	72 °C
(rs17576)	R:5'-GGTAGACAGGGTGGAGG-3'	5 min	30 s	30 s	30 s		7 min

Polymorphism	Restriction enzyme	Conditions	Fragment length (bp)
-1562C>T	SphI	37 °C for 16 h: PCR product 8 μL, 10×buffer 2 μL,	CC 435/435
(rs3918242)		H₂O₂ 10 μL, SphI 2 U	CT 435/188, 247
			TT 188, 247/188, 247
R279Q	SmaI	37 °C for 16 h: PCR product 8 μL, 10×buffer 2 μL,	GG 96, 181/96, 181
(rs17576)		H₂O₂10 μL, SmaI 2 U	GA 96, 181bp/277
			AA 277/277

Variables	ACS group (n=361)	Control group (n=432)	P value
Age (yeras)	61.53±10.47	59.56±9.52	0.204
TC (mmol/L)	4.41±1.16	4.16±0.99	0.010
TG (mmol/L)	1.97±1.08	1.94±0.65	0.753
LDL-C (mmol/L)	2.46±0.84	2.34±0.75	0.170
HDL-C (mmol/L)	0.97±0.25	1.31±0.67	<0.001
BMI (kg/m²)	27.10±3.59	24.99±3.17	<0.001
Smoking (no. %)	169 (46.8)	140 (32.4)	<0.001
Drinking (no. %)	135 (37.4)	173 (40.0)	0.446
Diabetes mellitus (no. %)	75 (20.8)	43 (10.0)	<0.001
Hypertension (no. %)	171 (47.4)	141 (32.6)	<0.001

MMP-9 polymorphisms	ACS group [n=361(%)]	Control group [n=437(%)]	OR (95% CI)	P value
-1562C>T
CC	269 (74.5)	368 (84.2)	1
CT	81 (22.4)	64 (14.7)	1.73 (1.204-2.491)	0.003
TT	11 (3.1)	5 (1.1)	3.01 (1.034-8.763)	0.034
CT+TT	92 (25.5)	69 (15.8)	1.82 (1.286-2.587)	0.001
C allele	619 (85.7)	800 (91.5)	1
T allele	103 (14.3)	74 (8.5)	1.80 (1.311-2.469)	<0.001
R279Q
RR	123 (34.1)	162 (37.1)	1
RQ	152 (42.1)	191 (43.7)	1.05 (0.764-1.439)	0.771
QQ	86 (23.8)	84 (19.2)	1.35 (0.921-1.974)	0.124
RQ+QQ	238 (65.9)	275 (62.9)	1.14 (0.852-1.526)	0.379
R allele	398 (55.1)	515 (58.9)	1
Q allele	324 (44.9)	359 (41.1)	1.17 (0.957-1.425)	0.127

Genotype	With 1 stenotic vessel	With 2 stenotic vessel	With 3 stenotic vessel	Total number
CC	125 (46.5)	104 (38.6)	40 (14.9)	269
CT+TT	37 (40.2)	41 (44.6)	14 (15.2)	92
Total	162 (44.9)	145 (40.2)	54 (14.9)	361