Matrix Metalloproteinase Gene Polymorphisms Research Articles

Matrix Metalloproteinase-3 Gene Polymorphisms Are Associated with Ischemic Stroke

Stroke is a heterogeneous disease caused by different pathogenic mechanisms. Several candidate genes for stroke have been proposed, but few have been replicated. Matrix metalloproteinases (MMPs) are expressed following stroke. We investigated the association of single nucleotide polymorphisms (SNPs) of the MMP3 gene with stroke in the Korean population. This study included 186 stroke patients [116 ischemic stroke (IS) and 70 intracerebral hemorrhage (ICH)] and 668 age-matched control subjects (267 for IS and 401 for ICH). Three SNPs [rs520540 (Ala362Ala), rs602128 (Asp96Asp), and rs679620 (Lys45Glu)] in the coding region of MMP3 were selected and genotyped by direct sequencing. HelixTree, SNPAnalyzer, SNPStats, and Haploview version 4.2 were used to analyze genetic data. Multiple logistic regression models (codominant, dominant, and recessive models) were conducted to evaluate odds ratio, 95% confidence interval, and P value. Three SNPs in the MMP3 gene were significantly associated with IS (P<0.05). The genotype distribution of 3 SNPs differed between the IS and control subjects. However, there was no association of the SNPs between the ICH and control. In analysis of gender, 3 SNPs were also associated with IS in female group (P<0.05). These SNPs remained significantly associated with IS after the Bonferroni correction for multiple testing (P(c)<0.05). Haplotype analysis revealed that no haplotypes were associated with IS or ICH. Overall, the results of our study demonstrate an association of the MMP3 gene with development of IS, and no association of MMP3 with ICH.

Matrix metalloproteinase-9 genetic variations affect MMP-9 levels in obese children

Matrix metalloproteinase-9 (MMP-9) is involved in the atherosclerotic process and functional polymorphisms in the MMP-9 gene affect MMP-9 expression/activity, and are associated with cardiovascular diseases. However, no study has tested the hypothesis that functional MMP-9 polymorphisms could affect MMP-9 levels in obese children. We investigated whether three MMP-9 gene polymorphisms (C-1562T (rs3918242), 90(CA)((14-24)) (rs2234681) and Q279R (rs17576)), or haplotypes, affect MMP-9 levels in obese children. We studied 175 healthy control children and 127 obese children. Plasma MMP-9, tissue inhibitor of MMPs (TIMP)-1 and adiponectin concentrations were measured using enzyme-linked immunosorbent assay. We found similar MMP-9 genotypes, allelic and haplotypes distributions in the two study groups (P>0.05). However, we found lower plasma MMP-9 concentrations in obese subjects carrying the CC or the QQ genotypes for the C-1562T and the Q279R polymorphisms, respectively, in obese children compared with children with the other genotypes, or with non-obese children with the same genotypes (all P<0.05). Moreover, we found lower MMP-9 levels and lower MMP-9/TIMP-1 ratios (which reflect net MMP-9 activity) in obese children carrying the H2 haplotype (which combines the C, H and Q alleles for the three polymorphisms, respectively) when compared with obese children carrying the other haplotypes, or with non-obese children carrying the same haplotype (P<0.05). Our findings show that MMP-9 genotypes and haplotypes affect MMP-9 levels in obese children and adolescents, and suggest that genetic factors may modify relevant pathogenetic mechanisms involved in the development of cardiovascular complications associated with obesity in childhood.

Interaction Between MMP-9 Gene Polymorphisms and Smoking in Relation to Myocardial Infarction in a Uighur Population

Matrix metalloproteinase 9 (MMP-9) plays a pivotal role in early atherosclerosis, vascular remodeling, and development of arterial plaque rupture. The potentially functional MMP-9 gene polymorphism may contribute to the susceptibility of myocardial infarction (MI). We aimed to investigate the association between the interaction of 2 single-nucleotide polymorphisms ([SNPs] -1562C>T and R279Q) of the MMP-9 gene and smoking with MI in a Uighur population of China. A case-control study composed of 384 coronary angiography proven patients with MI and 451 sex-matched and ethnically matched control participants were enrolled in the study. The genotypes of the 2 selected SNPs were determined by the method of polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP). Analysis of 2 SNPs, the frequency of -1562 CT and TT genotypes in MI group was significantly higher than in control group (25.52% vs 17.29%; P = .004). And the -1562 T allele showed significant association with MI (MI vs controls: 14.19% vs 9.31%; P = .002). R279Q locus did not show significant differences between patients and controls ( P > .05). Multiple logistic regression analysis showed that -1562 T allele (CT or TT genotype; odds ratio [OR] 1.31, 95% confidence interval [CI] 1.22-1.40; P = .004), the interaction between -1562 T allele and smoking (OR 4.42, 95% CI 2.74-7.13; P < .001), and the interaction between 279 Q allele and smoking (OR 2.07, 95% CI: 1.04-4.13; P = .021) were independent risk factors for MI. There findings suggest that MMP-9 -1562C>T polymorphism could be associated with the susceptibility to MI. Another SNP (R279Q) polymorphism was not significantly associated with MI. The -1562C>T or R279Q polymorphism of MMP-9 gene and smoking have a synergistic effect and are significantly associated with the risk of MI in Chinese Uighur population, respectively.

Association of matrix metalloproteinase (MMP-1, MMP-3 and MMP-9) and cyclooxygenase-2 gene polymorphisms and their proteins with chronic periodontitis

AimsThe objective of this study was to investigate the association amongst the single nucleotide polymorphisms of genes encoding for matrix metalloproteinase (MMP) 1, 3, 9 and cyclooxygenase-2 (COX-2) of subjects. Protein production of MMPs, COX-2 and Vascular Endothelial Growth Factor (VEGF) were also investigated. Methods280 chronic periodontitis patients and 250 periodontitis-free subjects were selected. DNA was extracted from blood samples of all patients, the polymorphic sites of the genes that encode for metalloproteinases and cyclooxygenase-2 were amplified using PCR, and digested with restriction enzymes. ELISA was used to determine the protein production of MMPs, COX-2 and VEGF. ResultsThe mean probing depth (PD) was 5.4mm and the clinical attachment loss (CAL) was 6.4mm in patients group with at least 2 years history. 2G/2G genotype of MMP-1, the periodontitis patients presented frequency of 28% and the control only showed 3%. 5A/5A genotype of MMP-3, the periodontitis patients presented higher frequency of 55% than the control 40%. C/C of genotype MMP-9, the periodontitis patients presented higher frequency of 51% than the control 17%. C/C of genotype COX-2, the periodontitis patients demonstrated 28% frequency and the control was 3%. ELISA analysis determined a significant difference (p<0.001) in protein production between patient and control samples for the bio-markers. 12 cases with suspicious genotype of MMPs and in COX-2 showed the serum level was the highest value between other C/C genotype. ConclusionsCombine genotype and serum expression of inflammatory mediators that may be a good bio-marker for diagnosis and prognosis of the periodontitis.

Matrix Metalloproteinase Pharmacogenomics in Non-Small-Cell Lung Carcinoma

Non-small-cell lung carcinoma demonstrated considerable variability in its chemoresponse. However, the prospect of individualized medicine holds high hopes for improving patient survival. The study of tumor and patient genetic profiles, relative to drug-related genes, may offer new opportunities for tailoring treatments. Matrix metalloproteinases (MMPs) are zinc-containing endopeptidases, which degrade the extracellular matrix and basement membrane, and process bioactive mediators involved in promoting aspects of tumor growth. Polymorphisms in MMP genes known to influence the protein-expression patterns has been shown to influence therapy outcomes by altering signaling pathways. In this article, we address the polymorphic association of MMPs in response to chemotherapy in non-small-cell lung carcinoma. Advances in genome technology and their comprehensive and systematic deployment to elucidate the genomic basis of MMP differences promise to ultimately enhance the efficacy of chemotherapy while reducing its toxicity for the treatment of various cancers.

Analysis of matrix metalloproteinase-9 gene polymorphism -1562 C/T in patients suffering from systemic sclerosis with and without ulcers

The objective of this study was to determine whether the matrix metalloproteinase-9 (MMP-9) rs3918242 single nucleotide polymorphism may confer susceptibility to systemic sclerosis (SSc) with and without ulcers in an Italian Caucasian population. The MMP-9 rs3918242 functional polymorphism was genotyped in 461 subjects of Italian Caucasian origin: 228 patients with SSc (92 with and 136 without ulcers) and 233 unrelated healthy individuals. The SNP under study was in Hardy-Weinberg equilibrium in the control population. Genotype and allele distributions between SSc patients, with or without ulcers, were not statistically significant (p>0.05). A significant increase of the genotype C/T was observed in male SSc patients without ulcers when compared to patients with ulcers (P=0.04). The MMP-9 rs3918242 functional polymorphism is not associated with susceptibility to SSc. However, the presence of the polymorphism may have a protective effect on the development of ulcers in SSc male patients.

Family Analysis of Linkage and Association of HLA-DRB1, CTLA4, TGFB1, IL4, CCR5, RANTES, MMP9 and TIMP1 Gene Polymorphisms with Multiple Sclerosis

Multiple sclerosis (MS) is a chronic inflammatory autoimmune disease of the central nervous system (CNS). Proteins of the immune system, as well as proteins that are involved in the infiltration of activated immune cells in the CNS, play an important role in the pathogenesis of MS. We investigated the association and linkage with MS of the following immune-system genes polymorphisms: HLA-DRB1,CTLA4,TGFB1,IL4,CCR5 andRANTES, as well as of the matrix metalloproteinase 9 (MMP9) and tissue inhibitor of metalloproteinase 1 (TIMP1) genes polymorphisms. For this purpose we used the transmission disequilibrium test (TDT). The group investigated was comprised of 100 nuclear families of Russian ethnicity, each consisting of an affected offspring and his nonaffected parents. It was found that HLA-DRB1*15alleleandMMP9*-1562C allele were transmitted from healthy heterozygous parents to affected children more frequently than alternative alleles (p = 0.02 andp = 0.04, respectively). Another family-based method, AFBAC (affected family-based control), showed MS association with HLA-DRB1*15, but not with theMMP9*-1562C allele.

Functional polymorphism of matrix metalloproteinase-9 (MMP-9) gene and response to lithium prophylaxis in bipolar patients

Matrix metalloproteinase 9 (MMP-9) has been implicated in a number of pathological conditions including cancer and heart diseases, and recently also in such neuropsychiatric disorders as schizophrenia and bipolar illness. Therefore, we investigated a possible association between functional polymorphisms of the MMP-9 gene and the response to lithium, the main mood-stabilizing drug in bipolar illness. One hundred and nine bipolar patients treated with lithium for at least 5 years were analyzed. The lithium response was assessed as--excellent: no affective episodes during lithium treatment; partial: 50% or more reduction in the episode index; no response: less than 50% reduction, no change or worsening in the episode index. The -1562C/T MMP-9 gene polymorphism (rs3918242) was assessed by PCR-RFLP method. Genotype distributions were not in Hardy-Weinberg equilibrium. No association was found between polymorphism studied and the quality of response to prophylactic lithium administration. The functional polymorphism of the MMP-9 gene, analyzed in this study, may not be associated with the treatment response to lithium in bipolar patients.

No evidence indicated that polymorphisms of the matrix metalloproteinases genes were associated with breast cancer risk: an update

We read with great interest the article by Zhou et al. [1] about the meta-analysis of four polymorphisms of the matrix metalloproteinases (MMP) genes in breast cancer risk. The results suggested that MMP-2-1306 C/T polymorphism was associated with the risk of breast cancer; and no statistical association was detected for MMP1 -1607 2G/1G polymorphism, MMP-3 -1171 6A/5A polymorphism and MMP-9 -1562 C/T. However, there were two methodological issues which should be addressed. First, the results presented in Table 3 were beyond understanding. Taking MMP-2 -1306 C/T polymorphism as an example, the pooled odds ratios (ORs) should be presented under co-dominant model (TT vs. CC; CT vs. CC), recessive model (TT vs. CT ? CC), or dominant model (TT ? CT vs. CC), respectively. Second, it was improper to set the statistical significant level to 0.01 for the deviation from Hardy–Weinberg equilibrium (HWE) in controls. Usually, a P \ 0.05 indicated the deviation from HWE in controls [2, 3]. Therefore, two studies [4, 5], which deviated from HWE in controls, included in their meta-analysis should be excluded. Considering the two methodological issues above, we re-investigated the association between four polymorphisms of MMP genes and breast cancer risk (Table 1). Our results indicated that four polymorphisms of MMP genes were not associated with breast cancer risk. Given the limited sample size for four polymorphisms, further studies with enough statistical power are necessary to clarify the association.

Genetic variation in the matrix metalloproteinase genes and diabetic nephropathy in type 1 diabetes

Genetic data support the notion that polymorphisms in members of the matrix metalloproteinase (MMP) family of genes play an important role in extracellular matrix remodeling and contribute to the pathogenesis of vascular disease. To identify novel genetic markers for diabetic nephropathy (DN), we examined the relationship between MMP gene polymorphisms and DN in the Genetics of Kidneys in Diabetes (GoKinD) population. Genotypic data from the Genetic Association Information Network (GAIN) type 1 DN project were analyzed for associations across 21 MMP genes in 1705 individual with type 1 diabetes, including 885 normoalbuminuric control subjects and 820 advanced DN case subjects. In total, we investigated the role of 1283 SNPs (198 genotyped SNPs and 1085 imputed SNPs) mapping to the MMP genes. We identified associations at several correlated SNPs across a 29.2 kb interval on chromosome 11q at the MMP-3/ MMP-12 locus. The strongest associations occurred at 2 highly-correlated SNPs, rs610950 (OR = 0.50, P = 1.6 × 10 −5) and rs1277718 (OR = 0.50, P = 2.1 × 10 −5). Further examination of this locus identified 17 SNPs (2 genotyped SNPs and 15 imputed SNPs) in complete linkage disequilibrium associated with DN ( P-values < 2.5 × 10 −4), including a non-synonymous SNP (rs652438, Asn357Ser) located in exon 8 of MMP-12 that significantly reduced the risk of DN among carriers of the serine substitution relative to homozygous carriers of asparagine (OR = 0.51; 95% CI = 0.37–0.71, P = 6.2 × 10 −5). Taken together, our study suggests that genetic variations within the MMP-3/ MMP-12 locus influence susceptibility of DN in type 1 diabetes.

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

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. 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. 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]. 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.

MMP-1 and MMP-3 polymorphism and arrhythmia recurrence after electrical cardioversion in patients with persistent atrial fibrillation

Cardiac extracellular matrix structure is largely under the control of the matrix metalloproteinases (MMPs) whose activity maintains a balance between connective tissue synthesis and degradation. MMP gene polymorphisms, by modifying the level of gene expression, may affect atrial structural remodelling and atrial fibrillation recurrence rate. The aim of this study was to evaluate the association between MMP-1 and MMP-3 polymorphisms and arrhythmia recurrence. We studied 74 persistent atrial fibrillation patients who underwent electrical cardioversion to restore sinus rhythm. In both patient and reference control groups, identification of MMP-1 and MMP-3 gene polymorphisms was performed by means of polymerase chain reaction according to standard techniques. Distribution of MMP-1 and MMP-3 genotypes and alleles were similar in atrial fibrillation patients and controls. During a 3-week follow-up period, 37 patients showed atrial fibrillation recurrences. Risk for atrial fibrillation recurrence significantly differed among groups (P = 0.0139) according to 5A and 1G allele presence. In particular, atrial fibrillation recurred in 62% of the patients carrying both 5A and 1G alleles (reference group) compared with no recurrence in patients carrying neither of them. We observed a significant relationship between MMP-1 and MMP-3 polymorphism and atrial fibrillation recurrences in patients with persistent atrial fibrillation. These findings suggest that genetic factors contribute to determine arrhythmic recurrence rate in persistent atrial fibrillation.

Genetic polymorphisms and plasma levels of matrix metalloproteinases and their relationships with developing acute myocardial infarction

Matrix metalloproteinases (MMPs) play an important role in early atherosclerosis, plaque rupture, extracellular matrix remodeling, and myocardial infarction (MI). MMP gene polymorphisms contribute to the risk of developing cardiovascular disease. We designed to investigate the association of acute MI (AMI) with a polymorphism in the human MMP-1, 2, 3, and 9 genes in Iranian patients with AMI. Genomic DNA of 400 enrolled patients with AMI and 200 controls was extracted from their blood samples. The -1607 1G/2G MMP-1, -1306 C/T MMP-2, -1171 5A/6A MMP-3, -1562 C/T MMP-9 polymorphisms were detected. Plasma levels of MMPs were analyzed. There are significant differences in MMP-3 '5A' allele and genotype in the patients with AMI comparing with controls. However, no significant differences were observed in MMP-1, 2, and 9 allele frequencies between the patients and controls. Differences between plasma levels of MMPs were significant in the patients than in controls. There were statistically significant differences between plasma MMP-3 in carriers of 5A allele compared with 6A allele. MMP-9 plasma levels were significantly higher in the carriers of -1306 TT and -1306 CT than CC. However, there were no statistically significant association between genetic variation of MMP-1, 2, and 3 in the patients and their plasma levels. These data suggest that MMP genotyping such as genetic polymorphism in MMP-3 might be helpful in determining susceptibility to AMI in Iranian patients. In addition, susceptibility to AMI might be related to MMP-9 gene expression, which affects its plasma levels.

Clinical Impact of MMP and TIMP Gene Polymorphisms in Gastric Cancer

Recent studies suggest that single-nucleotide polymorphisms (SNPs) within matrix metalloproteinase (MMP) genes and genes of tissue inhibitors of metalloproteinases (TIMPs) have an impact on the expression of these genes and on the prognosis for gastric cancer. Genomic DNA was extracted from paraffin-embedded tissues of 135 patients who were treated surgically for primary gastric carcinoma. Genotyping was performed for MMP-2(-1306C>T), TIMP-2(303C>T), and MMP-7(-181A>G). MMP-2 and TIMP-2 antigen expression in resected tumor tissues was detected immunohistochemically. Genotyping was correlated with antigen expression, histopathologic parameters, and prognosis. The SNPs did not correlate with tumor differentiation, pT, R category, or the classifications according to the International Union Against Cancer (UICC), the World Health Organization (WHO), and Laurén and Ming. A significant correlation was observed for TIMP-2(303C>T) with higher pN stages (p=0.01) and more distant metastasis (p=0.02) for patients with the CC genotypes. In univariate analysis, patients with the TIMP-2(303C>T) CC genotype had an inferior survival, that was not significant (p=0.2). However, among the gastric cancer patients in the present study, MMP-2(-1306C>T) significantly correlated with gender, with men having more CC genotypes than women (p=0.025). There were no significant correlations between genotype and protein levels of MMP-2 (p=0.766) and TIMP-2 (p=0.684). The TIMP-2(303C>T) CC genotype is associated with higher pN and pM categories and, in contrast to previous studies, with worse survival in gastric cancer.

Association of Matrix Metalloproteinase Gene Polymorphisms with Refractive Error in Amish and Ashkenazi Families

Matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) are involved in scleral extracellular matrix remodeling and have shown differential expression in experimental myopia. The genetic association of refractive error and polymorphisms in MMP and TIMP genes in Old Order Amish (AMISH) and Ashkenazi Jewish (ASHK) families was investigated. Individuals from 55 AMISH and 63 ASHK families participated in the study. Ascertainment was designed to enrich the families for myopia; the mean spherical equivalent (MSE) refractive error (SD) was -1.61 (2.72) D in the AMISH, and -3.56 (3.32) D in the ASHK. One hundred forty-six common haplotype tagging SNPs covering 14 MMP and 4 TIMP genes were genotyped in 358 AMISH and 535 ASHK participants. Association analyses of MSE and the spherical component of refraction (SPH) were performed separately for the AMISH and the ASHK. Bonferroni-corrected significance thresholds and local false discovery rates were used to account for multiple testing. After they were filtered for quality-control, 127 SNPs were included in the analyses. No polymorphisms showed statistically significant association to refraction in the ASHK (minimum P = 0.0132). In AMISH, two SNPs showed evidence of association with refractive phenotypes: rs1939008 (P = 0.00016 for SPH); and rs9928731 (P = 0.00026 for SPH). These markers were each estimated to explain <5% of the variance of SPH in the AMISH sample. Statistically significant genetic associations of ocular refraction to polymorphisms near MMP1 and within MMP2 were identified in the AMISH but not among the ASHK families. The results suggest that the MMP1 and MMP2 genes are involved in refractive variation in the AMISH. Genetic and/or environmental heterogeneity most likely contribute to differences in association results between ethnic groups.

Matrix metalloproteinase (MMP-9 and MMP-2) gene polymorphisms influence allograft survival in renal transplant recipients

Matrix metalloproteinases (MMPs), especially basement membrane-degrading MMP-9 and MMP-2, play an important role in immune-mediated tissue destruction of the allograft by allowing influx of leucocytes and mononuclear cells into the graft. The present study was, therefore, undertaken to investigate the association of functional polymorphisms in MMP-9 (836A>G, 1721G>C and 2003G>A) and MMP-2 (-735C>T) genes with risk of allograft rejection in renal transplant recipients of North India. Three hundred and six renal transplant recipients categorized into 228 non-rejecters and 78 rejecters were genotyped for MMP-9 and MMP-2 polymorphisms by polymerase chain reaction-restriction fragment length polymorphism methodology. A significant difference in genotype/allele frequencies was observed between healthy individuals in comparison to non-rejecters/rejecters for MMP-9 836A>G, MMP-9 2003G>A and MMP-2 -735C>T. Mutant allele carriers for MMP-9 2003G>A [GA+AA-; odds ratio (OR) = 0.45, 95% confidence intervals (95% CI) = 0.24-0.85, P = 0.014] and MMP-2 -735C>T (CT+TT-; OR = 0.40, 95% CI = 0.18-0.91, P = 0.029) demonstrated significantly reduced risk for allograft rejection. The mean time to first rejection episode was significantly higher in GA/AA and CT/TT genotype recipients for MMP-9 2003G>A (log P = 0.026) and MMP-2 -735C>T (log P = 0.003), respectively. Haplotypes with mutant alleles for MMP-9 1721C>G-2003G>A and mutant allele genotype combinations for both MMP-9 2003G>A and MMP-2 -735C>T conferred significantly reduced risk for allograft rejection. Mutant alleles for MMP-9 2003G>A and MMP-2 -735C>T are associated with reduced risk for allograft rejection and improved allograft survival in North Indian transplant recipients and could serve as an ideal marker to predict pre-transplant allograft outcome.

Association between polymorphisms of matrix metalloproteinase 11 (MMP-11) and Kawasaki disease in the Korean population

Aims This study was conducted to investigate the associations between single nucleotide polymorphisms (SNPs) of matrix metalloproteinases (MMPs) and Kawasaki disease (KD) in the Korean population. Main methods A total 0f 101 KD patients and 306 healthy controls were examined. MMP7 (rs10502001, G/A, Arg77His), MMP11 (rs738792, T/C, Ala38Val), MMP12 (rs652438, A/G, Ile357Val) and MMP26 (rs2499953, A/G, Lys43Glu) genes were genotyped from the genomic DNA using direct sequencing. The results were then analyzed using logistic regression models, adjusting for gender as covariates. Key findings The four SNPs were in Hardy–Weinberg equilibrium. Only the MMP11 polymorphism (rs738792) was associated with KD. The SNP (rs738792) showed a statistically significant association with KD in the codominant (OR = 1.61, 95% CI = 1.11–2.34, P = 0.011) and dominant (OR = 1.92, 95% CI = 1.21–3.06, P = 0.006) models. However, there was no association between polymorphisms of other MMP genes and KD. Significance Overall, the results of this study indicate that MMP11 polymorphism may be associated with KD in the Korean population.

Matrix metalloproteinase-9 polymorphism and risk of pelvic organ prolapse in Taiwanese women

Objective Matrix metalloproteinase-9 is known to play an important role in the pathophysiology of pelvic organ prolapse. We investigated whether the matrix metalloproteinase-9 gene polymorphisms were associated with pelvic organ prolapse by conducting a case–control association study in 92 women with pelvic organ prolapse and 152 women without pelvic organ prolapse. Study design Genotypes of the matrix metalloproteinase-9 gene polymorphisms (rs3918242, rs17576, and rs2250889) were determined by polymerase chain reaction, followed by restriction fragment length polymorphism analysis. Results There was significant difference between women with and without pelvic organ prolapse in the distribution of the matrix metalloproteinase-9 rs17576 genotypes evaluated. Using multivariable logistic regression, menopausal status, matrix metalloproteinase-9 rs17576 genotype AG, and matrix metalloproteinase-9 rs17576 genotype GG were significantly associated with pelvic organ prolapse. Conclusion The present study shows that the polymorphism of matrix metalloproteinase-9 rs17576 may be associated with pelvic organ prolapse.

Impact of ENPP1 and MMP3 gene polymorphisms on aortic calcification in patients with type 2 diabetes in a Korean population

Aims We investigated whether gene polymorphisms of Ecto-nucleotide pyrophosphatase/phosphodiesterase 1 ( ENPP1) and matrix metalloproteinase 3 ( MMP3) are associated with increased vascular calcification in patients with type 2 diabetes (T2D) and evaluated whether serum MMP3 and osteoprotegerin (OPG) levels are related to calcification. Methods This study included 464 subjects: 269 patients with T2D and 195 healthy controls in South Korea. We genotyped subjects for four single nucleotide polymorphisms (SNPs): ENPP1 K121Q, ENPP1 A/G+1044TGA, MMP3 −709A>G and MMP3 −1475G>A. The presence or absence of calcifications in the aortic arch was assessed by plain chest radiography. Results The SNPs ENPP1 K121Q and MMP3 −709A>G showed significant associations with T2D ( P = 0.001 and P = 0.004). The SNP ENPP1 K121Q showed a significant association with aortic arch calcification in T2D ( P = 0.036). Serum OPG levels were significantly higher in T2D patients than in the control group ( P < 0.001). However, serum MMP3 levels were significantly lower in T2D patients than in the control group ( P < 0.001). Conclusions Our study demonstrates that the ENPP1 K121Q and MMP3 −709A>G polymorphisms are associated with T2D, and that the ENPP1 Q allele is associated with increased aortic arch calcification in a Korean population.

Bladder cancer risk associated with genotypic polymorphism of the matrix metalloproteinase-1 and 7 in North Indian population.

Matrix metalloproteinases (MMPs) contribute to tumor invasion and microenvironment, hence are associated with bladder cancer risk. We therefore, tested whether polymorphisms in MMP genes modify the risk of bladder cancer (BC) and whether smoke exposure modifies this risk.Genotyping was performed in 200 BC patients and 200 controls by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). MMP1-1607 2G/2G and MMP7-181 GG genotype were associated with increased risk of BC (p <0.001; OR, 3.04; 95% CI1.71–5.39 and p, 0.005; OR, 2.38; 95% CI1.30–4.34) respectively. Smokers in BC patients showed significant increased risk for the same SNPs (p, 0.006; OR, 3.20; 95% CI1.40–7.31 and p, 0.009; OR, 2.85; 95% CI1.30–6.23 respectively). Haplotype analysis too revealed significant association with G/2G of MMP1-519-1607 (p < 0.001; OR, 2.62; 95% CI1.68–4.09). The 2G allele carrier (1G/2G + 2G/2G) of MMP1-1607 showed a protective effect and high recurrence free survival in Bacillus Calmette-Guerin (BCG) treated non muscle invasive BC (NMIBC) patients (log rank p, 0.030). Our datasuggested that MMP11607 2G and MMP7181 G allele were associated with high risk of BC, which was quite evident amongst smokers too. BCG treated NMIBC patients reflected protective effect for 2G allele carrier (1G/2G+2G/2G) of MMP1-1607. This study provided new support for the association of MMP1-1607 and MMP7-181 in bladder cancer development, the tumorigenic effect of which was observed to be more enhanced in case of tobacco exposure.