Cardiovascular Risk and Matrix Metalloproteinase Polymorphisms: Not Just a Simple Substitution.
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ABSTRACT:
SUBMITTER: Spinale FG
PROVIDER: S-EPMC5726789 | biostudies-literature | 2017 Dec
REPOSITORIES: biostudies-literature
Publications
Cardiovascular Risk and Matrix Metalloproteinase Polymorphisms: Not Just a Simple Substitution.
Spinale Francis G FG Sapp Ashley A AA
Circulation. Cardiovascular genetics 20171201 6
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Project description:Matrix metalloproteinases (MMP) degrade various components of the extracellular matrix, and their overexpression has been implicated in tumor progression. Nonsynonymous single nucleotide polymorphisms (SNPs) lead to amino acid substitutions that can alter the function of the encoded protein. We evaluated the associations of six nonsynonymous SNPs in the MMP3, MMP8, and MMP9 genes with skin cancer risk in a nested case-control study of Caucasians within the Nurses' Health Study among 218 melanoma cases, 285 squamous cell carcinoma (SCC) cases, 300 basal cell carcinoma (BCC) cases, and 870 normal controls. We observed that the MMP9 Arg668Gln polymorphism was significantly associated with a decreased risk of SCC. Compared with the Arg/Arg group, the multivariate odds ratio was 0.67 (95% confidence interval, 0.47-0.97) for the Arg/Gln group and 0.21 (95% confidence interval, 0.05-0.97) for the Gln/Gln group (P(trend) = 0.004). We did not observe any association of this SNP with the risks of melanoma and basal cell carcinoma. No associations were found for other SNPs with skin cancer risk. This study provides evidence for the contribution of the MMP9 Arg668Gln to SCC development.
| S-EPMC2664625 | biostudies-literature
Project description:Background/aimMatrix metalloproteinase-1 (MMP-1) expression has been documented as an influential contributor to the intricate milieu of allergic airway inflammation, tissue remodeling, and the exacerbation of asthma's severity. However, the genetic role underlying MMP-1 in the context of asthma has remained enigmatic, with its full implications yet to be unveiled. Considering this, our research was designed to investigate the association of MMP-1 -1607 rs1799750 and the propensity for asthma severity.Patients and methodsAs a case-control investigation, our study enrolled 198 individuals diagnosed with asthma and age- and sex-matched 453 non-asthmatic controls. The genotypes of MMP-1 rs1799750 were determined utilizing the polymerase chain reaction-restriction fragment length polymorphism methodology.ResultsThe frequency distributions of 2G/2G, 1G/2G and 1G/1G genotypes at MMP-1 rs1799750 were 49, 42.9, and 8.1%, respectively, among the patients with asthma. This pattern was not different from that of controls (43.7, 46.8, and 9.5%, respectively) (p for trend=0.4486). The allelic frequency pertaining to the variant 1G allele within the asthma group was 29.5%, with a non-significant disparity compared to the 32.9% in the control group (p=0.2596). Noticeably, there was a positive association between MMP-1 rs1799750 2G/1G and 1G/1G genotypes with asthma severity (p=0.0060).ConclusionOur research indicated that the presence of MMP-1 rs1799750 1G allele might not be the sole arbiter of an individual's susceptibility to asthma, yet its potential to function as a discerning prognostic marker for the severity of asthma emerged as a noteworthy finding deserving attention and further exploration.
| S-EPMC10756462 | biostudies-literature
Project description:The matrix metalloproteinase (MMP) family degrade extracellular matrix and mediate pathways including apoptosis, angiogenesis and immunity. We studied the association between four MMP polymorphisms within three MMP genes and esophageal adenocarcinoma (EA) risk and prognosis. A total of 313 EA cases and 455 age and gender frequency-matched controls were genotyped for MMP1 1G/2G, MMP3 6A/5A, MMP12 -82A/G and MMP12 1082A/G. The association between individual MMP polymorphisms and EA risk was evaluated using regression models and adjusted for age, gender, adult body mass index and smoking status. Haplotype analysis was performed to investigate the combined effect of all four linked MMP polymorphisms and EA risk. The MMP1 and MMP3 polymorphisms were associated with increased EA risk: MMP1 1G/2G and 2G/2G had adjusted odds ratios of 1.46 [95% confidence interval 1.0-2.1; P = 0.04] and adjusted odds ratio 1.83 (1.2-2.8; P = 0.005), respectively, whereas MMP3 6A/5A had adjusted odds ratio 1.40 (95% confidence interval 1.0-2.1; P = 0.09) and MMP3 5A/5A had 1.61 (95% confidence interval 1.0-2.5; P = 0.03). Two MMP haplotypes [MMP1-MMP3-MMP12 (-82) 2G-5A-A (adjusted odds ratio 1.36, 95% confidence interval 1.0-1.8; P = 0.03) and 2G-5A-G (adjusted odds ratio 1.70, 95% confidence interval 1.1-2.6; P = 0.01)] were also associated with increased EA risk. The relationship between BE cases with the same set of controls was similar. No association was identified between the MMP polymorphisms and overall survival or progression free survival of patients with EA. MMP1, MMP3 and possibly MMP12 -82A/G polymorphisms and their haplotypes are associated with increased EA risk.
| S-EPMC2675656 | biostudies-literature
Project description:Matrix metalloproteinase-9 (MMP9) is a protease associated with degradation of collagen and elastin. Because increased MMP9 activity in vaginal tissue has been associated with pelvic organ prolapse (POP), we sought to comprehensively estimate MMP9 genetic variants and the risk for advanced prolapse.This is a candidate gene association study of women with stage III-IV prolapse (case group, n=239) and women with stage 0-1 prolapse (control group, n=197). We attempted to oversample "extreme" phenotypes, including younger women with severe prolapse and older women without prolapse, in an attempt to concentrate the genetic effect. We used a linkage disequilibrium tagged approach to identify single nucleotide polymorphisms in MMP9 to evaluate in our study. To minimize potential confounding by race, our analysis focused on non-Hispanic white women. We performed multivariable logistic regression to estimate the association between MMP9 single nucleotide polymorphisms and case-control status, adjusting for age and vaginal parity.Women with advanced prolapse were slightly younger (64.8 ± 10.3 compared with 69.0 ± 10.2 years, P<.001) and more likely to have had one or more vaginal deliveries (96.6% compared with 82.2%, P<.001) when compared with control participants. Eight single nucleotide polymorphisms were assessed, which represented 93% coverage of the MMP9 gene. Of these, two were associated with advanced prolapse: 1) rs3918253 (adjusted odds ratio [OR] 0.64, 95% confidence interval [CI] 0.41-1.0, P=.05); and 2) rs3918256 (adjusted OR 0.64, 95% CI 0.41-1.01, P=.05).MMP9 is a biologically plausible candidate gene for POP given our results.
| S-EPMC3427536 | biostudies-literature
Project description:Growing evidences show that matrix metalloproteinase-1 (MMP1) plays important roles in tumorigenesis and cancer metastasis. The interactions between MMP1-1607 1G>2G polymorphism and risk of gastric cancer (GC) have been reported, but results remained ambiguous. To determine the association between MMP1-1607 1G>2G polymorphism and risk of GC, we conducted a meta-analysis and identified the outcome data from all the research papers estimating the association between MMP1-1607 1G>2G polymorphism and GC risk, which was based on comprehensive searches using databases such as PubMed, Elsevier Science Direct, Excerpta Medica Database (EMBASE), and Chinese National Knowledge Infrastructure (CNKI). The fixed-effects model was used in this meta-analysis. Data were extracted, and pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated. In this meta-analysis, six studies involving 1,377 cases and 1,543 controls were included. We identified the significant association between MMP1-1607 1G>2G polymorphism and GC risk for allele model (OR =1.05; 95% CI, 1.01-1.08), for dominant model (OR =1.11; 95% CI, 1.08-1.15), and for recessive model (OR =1.06; 95% CI, 0.98-1.14). In summary, our analysis demonstrated that MMP1-1607 1G>2G polymorphism was significantly associated with an increased risk of GC.
| S-EPMC4574801 | biostudies-literature
Project description:BACKGROUND: Matrix metalloproteinase (MMP) is involved in the upper airway remodeling process. We hypothesized that genetic variants of the MMP-9 gene are associated with cases of chronic rhinosinusitis with nasal polyposis. METHODS: We conducted a case-control study where 203 cases of chronic rhinosinusitis with nasal polyposis and 730 controls were enrolled. Three tagging single nucleotide polymorphisms (SNPs) and one promoter functional SNP rs3918242 were selected. Hardy-Weinberg equilibrium (HWE) was tested for each SNP, and genetic effects were evaluated according to three inheritance modes. Haplotype analysis was also performed. Permutation was used to adjust for multiple testing. RESULTS: All four SNPs were in HWE. The T allele of promoter SNP rs3918242 was associated with chronic rhinosinusitis with nasal polyposis under the dominant (nominal p = 0.023, empirical p = 0.022, OR = 1.62) and additive models (nominal p= 0.012, empirical p = 0.011, OR = 1.60). The A allele of rs2274756 has a nominal p value of 0.034 under the dominant model and 0.020 under the additive model. Haplotype analysis including the four SNPs showed a global p value of 0.015 and the most significant haplotype had a p value of 0.0045. We did not see any SNP that was more significant in the recurrent cases. CONCLUSIONS: We concluded that MMP-9 gene polymorphisms may influence susceptibility to the development of chronic rhinosinusitis with nasal polyposis in Chinese population.
| S-EPMC2896930 | biostudies-literature
Project description:Matrix metalloproteinase-2 (MMP-2) is a well-known mediator of cancer metastasis but is also thought to be involved in several aspects of cancer development, including cell growth and inflammation. We comprehensively characterized genetic variation across the MMP-2 gene and evaluated associations with breast cancer risk using a two-phase (phase 1 and phase 2) study design. A total of 39 polymorphisms were genotyped among 6,066 Chinese women participating in the Shanghai Breast Cancer Study, a population-based case-control study. Two MMP-2 promoter polymorphisms were found to have consistent results between phase 1 and phase 2 participants, and to be significantly associated with breast cancer risk among all genotyped participants. Minor allele homozygotes for rs11644561 (G/A) were found to have a decreased risk of breast cancer [odds ratio (OR), 0.6; 95% confidence interval (CI), 0.3-1.0] compared with major allele homozygotes, as were minor allele homozygotes for rs11643630 (T/G) compared with major allele homozygotes (OR, 0.8; 95% CI, 0.7-1.0). When analyzed together, a rare haplotype (4.4%) with both rs11644561 A and rs11643630 G was found to have a significantly reduced risk of breast cancer (OR, 0.6; 95% CI, 0.4-0.8). In addition, rare allele homozygotes for rs243865 (-1306 C/T) tended to have an increased risk of breast cancer (OR, 1.4; 95% CI, 0.9-2.4). Together, these findings support a role for MMP-2 genetic variation in breast cancer susceptibility.
| S-EPMC2747044 | biostudies-literature
Project description:Published data on the association between MMP-9 polymorphisms (-1562 C > T, rs3918242; Gln279Arg, rs17576 Arg668Gln, rs17577) and asthma susceptibility are inconclusive. To derive a more precise estimation of this association, a meta-analysis was performed. A literature search was conducted in PubMed, Web of Science, EMBASE, Wanfang, and China National Knowledge Infrastructure (CNKI) databases to identify eligible studies. The pooled odds ratios (ORs) and corresponding 95% confidence intervals (CIs) were used to calculate the strength of association. Sensitivity analysis was performed to evaluate the influence of individual studies on the overall effect estimates, and funnel plots and Egger's test were inspected for indication of publication bias. Seven studies with 1592 asthma patients and 1987 controls were finally identified. Overall, we found no significant association between -1562 C > T, rs3918242 polymorphism, and asthma susceptibility in any of the genetic model comparisons. After categorizing studies into different subgroups on the basis of ethnicity and age, there is still no significant association. For the Gln279Arg, rs17576 polymorphism, there seems to be a significant association in the allelic genetic model in regard to the P value (OR = 1.11, 95% CI = 1.00-1.22, I 2 = 0%, P (Z)=0.044); however, the value of lower 95% CI is 1.0. For the Arg668Gln, rs17577 polymorphism, a high significant association was observed in the dominant model comparison (OR = 1.65, 95% CI = 1.28-2.11, I 2 = 22.50%, P (Z)=0), recessive model comparison (OR = 2.40, 95% CI = 1.23-4.72, I 2 = 0%, P (Z)=0.011), homozygote genotype comparison (OR = 2.69, 95% CI = 1.36-5.33, I 2 = 0%, P (Z)=0.004), and allelic genetic model (OR = 1.59, 95% CI = 1.29-1.97, I 2 = 36.9%, P (Z)=0). Sensitivity analysis demonstrated the stability of our results, and publication bias was not evident. The present meta-analysis suggests that MMP-9 Arg668Gln, rs17577 polymorphism may be the risk factor for asthma susceptibility.
| S-EPMC6410464 | biostudies-literature
Project description:The current study aimed to investigate the relations of three single nucleotide polymorphisms of matrix metalloproteinase-9 gene, and single nucleotide polymorphisms-smoking interaction to subarachnoid hemorrhage risk. The optimal pattern of the interaction among single nucleotide polymorphisms and smoking was selected by generalized multifactor dimensionality reduction. The association between the three single nucleotide polymorphisms within the matrix metalloproteinase-9 gene was analyzed by logistic regression test. As well as genetic risk of subarachnoid hemorrhage interactions with smoking, the risk of subarachnoid hemorrhage in carriers with the rs3918242 (T) was significantly higher than in carriers carrying CC (genotype: CT + TT vs. CC), adjusted OR (95% CI) = 1.58 (1.25-2.03), and in carriers carrying rs17576- (genotype: AG + GG vs. AA), adjust OR (95% CI) = 1.62 (1.19-2.13). However, after adjusting for covariates, we did not find any direct association between rs17577 and subarachnoid hemorrhage risk. The generalized multifactor dimensionality reduction model shows a potential relation between rs3918242 and smoking risk for subarachnoid hemorrhage ( P = 0.0010). After covariates adjustment, current smokers with rs3918242-CT or TT genotype, compared to never-smokers with rs3918242-CC genotype, OR (95% CI) = 2.57 (1.74-3.46), have a higher subarachnoid hemorrhage risk. Our study showed that the rs3918242 (T) and rs17576 (G), the cross reaction between rs3918242 and smoking increased the risk of subarachnoid hemorrhage. Impact statement Matrix metalloproteinase-9 ( MMP-9) is a possible candidate gene for some diseases, including metabolic syndrome, stroke, coronary artery disease (CAD). But to date, limited data focused on the relationship between MMP-9 gene SNPs and SAH susceptibility. The purpose of this study was to evaluate SNPs of MMP-9 gene and their interaction with environmental factors with SAH risk based on a Chinese population.
| S-EPMC5956669 | biostudies-literature
Project description:BackgroundChronic hepatitis C (CHC) virus infection is one of major risk factors of hepatocellular carcinoma (HCC) in Egypt, which is a major cause of cancer mortalityin the world. Matrix metalloproteinase-11 (MMP-11) has an important role in tumor migration and metastasis. Therefore, this study aimed to determine relation between MMP-11 gene polymorphisms and risk of HCC development among Egyptian cirrhotic patients.Subjects and methodsTwo hundred and sixty patients were included, 140 of them with HCC on top of CHC and 120 patients with post CHC liver cirrhosis (LC) as well as 140 subjects were enrolled in the study as healthy controls. Two single nucleotide polymorphisms (SNPs) rs738791 and rs738792 for MMP-11 gene were done using real-time PCR.ResultsCombination of CT and TT allele of rs738791 genotypes was more significantly frequent in HCC compared to LC patients and controls, however, a higher frequency of T allele was found in HCC patients compared to LC and controls. In spite of lake of significant difference between patient groups regarding the rs738792 genotypes, the CC genotype was considered a risk of developing portal vein thrombosis, and was associated with advanced tumor stage, increased tumor size, higher Cancer of the Liver Italian Program [CLIP] score, more advanced Barcelona stage [D] and with child Pugh class [C].ConclusionGenetic variations in MMP-11 may be implicated in post HCV-HCC development and might be dependable biomarkers for HCC progression.
| S-EPMC8046319 | biostudies-literature