MMP1 Rs1799750 Research Articles

The 1G/1G+1G/2G Genotypes of MMP1 rs1799750 Are Associated with Higher Levels of MMP-1 and Are Both Associated with Lipodystrophy in People Living with HIV on Antiretroviral Therapy.

In HIV-infected patients, antiretroviral therapy (ART) is associated to adipose tissue redistribution known as lipodystrophy (LD). This study aimed at verifying the association between the polymorphism of the MMP1 gene (rs1799750) (1G/2G) and the serum levels of matrix metalloproteinase 1 (MMP-1) with LD and its subtypes in people living with HIV on ART. This is a cross-secional study. LD was self-reported. The determination of the MMP1 rs1799750 gene polymorphism was performed by real-time PCR, and the serum concentrations of MMP-1 were quantified by the enzyme-linked immunosorbent assay (ELISA) method. Of 404 participants, 204 (51%) were diagnosed with LD, of whom 89 (43%) had mixed lipodystrophy (ML), 72 (35%) had lipohypertrophy (LH), and 43 (22%) had lipoatrophy (LA). There was an association between the genotypes 1G/1G+1G/2G and higher serum levels of MMP-1 (p = .025). There was no association of MMP1 (1G/2G) with LD. Other factors associated with LD were current CD4 ≤ 350 [odds ratio (OR) = 4.85, confidence interval (CI) = 1.78-47.99, p = .0033] and serum MMP-1 levels >6.81 (OR = 2.67, CI = 1.21-6.08, p = .0165). Factors associated with ML: current CD4 ≤ 350 (OR = 5.59, CI = 1.69-20.39, p = .006); with LH: number of antiretroviral regimens used: 2 (OR = 2.06, CI = 1.01-4.20, p = .0460) and 3+ (OR = 2.09, CI = 1.00-4.35, p = .0477), and current CD4 ≤ 350 (OR = 2.08, CI = 1.00-4.24, p = .0461); and with LA: current viral load >40 (OR = 2.52, CI = 1.03-5.91, p = .0372) and current use of zidovudine (OR = 2.97, CI = 1.32-6.54, p = .0074). Higher levels of MMP-1 were associated with genotypes 1G/2G+1G/1G and with LD. Other individual risk factors were independently associated with LD, and its subtypes, suggesting that the pathogenesis itself is differently manifested for each type of LD.

Peculiarities of Immune Regulation in Men of Perm Region with Atherosclerosis Related to Polymorphism of Candidate Genes.

The study examined peculiarities of immune regulation and associated polymorphic variants of candidate genes in men with atherosclerosis in Perm region. The revealed deficiency of CD127 lymphocytes and Annexin V-FITC+7AAD- cells, as well as enhanced level of CD3+CD4+ lymphocytes against the background of variant alleles of candidate genes FAS (rs1159120), CPOX (rs1131857) and wild-type alleles SULT1A1 (rs9282861), MMP9 (rs17576) are responsible for peculiar features of hereditary determination and pathogenesis of atherosclerosis in examined sample (p<0.05). The genetically determined degradation of extracellular matrix in vascular wall and implication of regulated Fas/APO1 apoptosis in the development of progressive atherosclerotic lesions indicate important role of immune system in atherogenesis. The revealed immunological and genetic features are recommended as the markers for early diagnosis of atherosclerosis and its prevention in men of Perm region.

Investigation of association between genetic polymorphisms of MMP2, MMP8, MMP9 and TIMP2 and development of varicose veins in the Slovak Population - pilot study.

Matrix metalloproteinases (MMPs) are a family of zinc-dependent metalloendopeptidases that degrades extracellular matrix (ECM) components. MMPs are associated with venous wall remodelling, proliferation, migration, phenotypic and functional transformation of vascular smooth muscle cells and ECM organization under the physiological and pathophysiological conditions. We investigated possible association of genetic promoter polymorphisms of MMP2 (rs243866), MMP8 (rs11225395), MMP9 (rs3918242) and TIMP2 (rs8179090) to varicose veins development in the Slovak population. Genomic DNA from 276 Slovak individuals (138 cases, 138 controls) was genotyped for selected SNPs (rs243866, rs11225395, rs3918242 and rs8179090) using the PCR-RFLP analysis. The data were analysed by chi-squared (chi2) test, logistic regression, and Mann-Whitney test. The risk of varicose veins development was evaluated in dominant, codominant and recessive genetic models. The statistical evaluation of selected polymorphisms in patients in all three genetic models has not shown a significant risk of varicose veins development. Our study has not shown the association between selected polymorphisms and increased risk of varicose veins development in Slovak population. More evidence with broaden sample size is needed.

Functional Polymorphism of MMP9 and BDNF as Potential Biomarker of Auditory Neuroplasticity in Prelingual Deafness Treatment With Cochlear Implantation-A Retrospective Cohort Analysis.

Genetic biomarkers of neuroplasticity in deaf children treated with cochlear implantation (CI) might facilitate their clinical management, especially giving them better chances of developing proficient spoken language. We investigated whether carrying certain variants of the genes encoding matrix metalloproteinase MMP9 and neurotrophin brain-derived neurotrophic factor (BDNF), involved in synaptic plasticity, can be taken as prognostic markers of how well auditory skills might be acquired. Association analysis of functional MMP9 rs3918242 and BDNF rs6265 variants and the child’s auditory development measured at CI activation and 1, 5, 9, 14, and 24 months post CI activation with LittlEARS Questionnaire (LEAQ) was conducted in a group of 100 children diagnosed with DFNB1-related deafness, unilaterally implanted before the age of 2 years. Statistical analysis in the subgroup implanted after 1 year of life (n = 53) showed significant association between MMP9 rs3918242 and LEAQ scores at 1 month (p = .01), at 5 months (p = .01), at 9 months (p = .01), and at 24 months (p = .01) after CI activation. No significant associations in the subgroup implanted before 1 year of life were observed. No significant associations between the BDNF rs6265 and LEAQ score were found. Multiple regression analysis (R2 = .73) in the subgroup implanted after 1 year of life revealed that MMP9 rs3918242 was a significant predictor of treatment outcome. In conclusion, C/C rs3918242 MMP9 predisposes their deaf carriers to better CI outcomes, especially when implanted after the first birthday, than carriers of C/T rs3918242MMP9.

Polymorphisms of matrix metalloproteinase-7 and -9 are associated with oral tongue squamous cell carcinoma.

Matrix degradation is an important event in the progression, invasion and metastasis of malignant head and neck lesions. Imbalances, mutations and polymorphisms of MMPs and their inhibitors are observed in several cancer subtypes. The aim of this study was to evaluate the association of the MMP-7 gene promoter (181 A/G) and MMP-9 (-1562 C/T) polymorphisms in oral tongue squamous cell carcinoma (OTSCC). MMP-7 (rs11568818) and MMP-9 (rs3918242) single-nucleotide polymorphisms (SNPs) were genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis in 71 cases of OTSCC. Normal tissue specimens were obtained from 60 healthy volunteers to serve as the control. The MMP-7 G allele and MMP-9 T allele were more frequent in the OTSCC group than the control group, but only when these two SNPs were taken together was a significant association found with the nodal metastasis of OTSCC (p < 0.001). Based on our results, SNPs in the promoter region of MMP-7 and MMP-9 appear to be associated with greater risk of developing OTSCC, and with a higher propensity to form metastatic tumors. In this respect, molecular studies investigating polymorphisms may be useful in predicting tumor behavior.

Contribution of Matrix Metalloproteinase-1 Genotypes to Colorectal Cancer in Taiwan.

Matrix metalloproteinase-1 is responsible for extracellular matrix regulation, and its genetic role in colorectal cancer (CRC) is unclear. The aim of the study was to investigate the contribution of Matrix metalloproteinase-1 genotypes to CRC risk in Taiwan. A total of 362 cases and 362 controls were included and their MMP-1 -1607 (rs1799705) genotypes were examined. The environmental factors and clinical-pathological records were also analyzed. The genotypic frequency of MMP-1 rs1799750 were different between the CRC and control groups (p for trend=0.0083). 1G/2G and 1G/1G were associated with lower risk (p=0.0438 and 0.0030, adjusted OR=0.73 and 0.54, 95%CI=0.54-0.90 and 0.37-0.83). Among non-smokers, those with 1G/2G and 1G/1G genotypes were at 0.70- and 0.48-fold odds of having CRC. Among non-alcohol drinkers, people with 1G/2G and 1G/1G genotypes were at 0.71- and 0.54-fold odds. The 1G/1G genotype were statistically lower among CRC patients with lymph node metastasis (7.2%) than those without (19.0%). The genotypes at MMP-1 rs1799705 play a role in determining susceptibility to CRC risk in Taiwan.

Genetic Polymorphisms and the Risk of Diabetic Foot: A Systematic Review and Meta-Analyses.

Diabetic foot (DF) is a dangerous complication of diabetes. The aim of the study was to synthesize all the published single nucleotide polymorphisms (SNPs) of DF to objectively evaluate the relationship of SNPs and DF risks. The HuGE database and CNKI were searched for eligible publications on genetic polymorphisms and the risk of DF systematically. The quality of literatures was evaluated by the Newcastle-Ottawa scale. Pooled odds ratios with a 95% confidence interval for SNPs were evaluated through 3 genetic models. Citing 29 different polymorphisms from 24 articles and the study met our selection criteria. There were 24 polymorphisms summarized systematically, and 5 merged polymorphisms for a meta-analysis: 9 positively associated with DF: HIF-1α rs11549465, TNF-α rs1800629, TLR-9 rs5743836, FIB rs6056, HSP70-2437C/T, VDR rs2228570, LOX rs1800449, ITLN1 rs2274907, and OPG rs2073617, but OPG rs3134069 was not a risk factor in DF; 6 negatively associated with DF: VEGF rs833061 and rs2010963, MCP-1 rs1024611, SDF-1 rs1801157, SIRT1 rs12778366, and OPG rs2073617. In addition, 13 polymorphisms were not associated with DF: MMP-9 rs3918242, eNOS rs1799983, VEGF rs3025039, -7C/T, rs1570360, rs13207351, and rs699947, IL-6 rs1800795, HIF-1α rs11549467, TNF-α rs361525, TLR-2 rs3804100, SIRT1 rs3758391, and TIMP-1 rs2070584. The study provided some evidence for SNPs to the development of diabetic foot. The meta-analysis showed that rs1024611 of MCP-1 may be regarded as a protective factor, especially in Asian populations. Other loci indicated inconsistent results.

Matrix metalloproteinase (MMP)-1 and MMP-3 gene variations affect MMP-1 and -3 serum concentration and associates with breast cancer.

Matrix metallopeptidases (MMPs) 1 and 3 have been shown to contribute to the initiation, and progression of different cancers, including breast cancer (BC). In this study, we aimed to examine the relations between polymorphisms of MMP1 (rs1799750) and MMP3 (rs632478) and their circulating levels with BC. The polymorphisms were genotyped by PCR-based Restriction Fragment Length Polymorphism (RFLP) and Allele-Specific PCR (AS-PCR) among 100 patients and 100 controls. MMP1 and MMP3 serum levels were measured by enzyme-linked immunosorbent assay (ELISA). Genotype distributions of MMP1 and MMP3 genes showed significant difference between patients and controls. The distribution of 2G/2G, 1G/2G and 1G/1G genotypes for MMP1 was 74%, 2% and 24% in the patients and 38%, 2% and 60% in the controls, respectively (P = 0.0001). For MMP3 the distribution of C/C, A/C and A/A genotypes was 28%, 54% and 18% in patients and 48%, 40% and 12% in controls, respectively (P = 0.01). For MMP1, the 2G/2G genotype was linked with a higher risk of BC when compared with that of the 1G/1G genotype (OR = 4.86; 95% CI = 2.63-8.99; P = 0.0001). For MMP3, in co-dominant model, there was a higher risk of BC in A/A and A/C genotype carriers (A/A: OR = 2.57; 95% CI = 1.08-6.11; P = 0.03) (A/C: OR = 2.31 95% CI = 1.24-4.30; P = 0.008). We also showed that MMP1 and MMP3 serum level was significantly increased in BC patients compared to controls. MMP1 and MMP3 genetic variations and their circulating levels are both significantly related to BC.

Comparative analysis of polymorphic variants of IL-17A and MMP-1 genes with the risk of developing chronic periodontitis in petrochemical workers

The susceptibility to the development and progression of inflammatory periodontal diseases, which depends on genetic and external factors (smoking, stress, oral hygiene), varies widely. In the development of these diseases, an important role is played not only by the presence of periodontal pathogenic microorganisms, but also by the presence of congenital or acquired immunodeficiency, immunoregulatory defects. The immune system plays a key role in the physiological and pathological processes of periodontal tissues. In this regard, IL17, produced by CD4+ Th cells, which has both Pro-inflammatory and protective activity, is of particular interest in the pathogenesis of periodontitis. The aim of study was to identify the relationship between polymorphic loci of the IL-17A (rs2275913) and MMP-1 (rs1799750) genes and clinical manifestations of chronic periodontitis in petrochemical workers. Dental examination was performed in 92 ethylene oxide production workers with chronic periodontitis and 74 patients with chronic periodontitis who did not come into contact with chemical factors (control group). Genotyping of polymorphisms rs2275913 of the IL17A gene and rs1799750 of the MMP1 gene was performed by allele-specific real-time polymerase chain reaction (PCR). Hygienic assessment of the degree of air pollution of the working area with harmful substances was carried out by gas chromatography according to the guidelines for the determination of harmful substances in the air № 5098-89, № 3119-84. When comparing the results of studies of both groups, there were no statistically significant differences in the frequency distributions of allelic variants and genotypes of the IL-17A and MMP-1 genes. The AA/AG genotypes of the IL-17A gene were associated with an increased risk of severe disease compared to the GG genotype in workers in the main group (OR=6.1; 95% CI 1.33-28.5; p=0.021) and in the control group (OR=7.26; 95% CI 1.34-39.25; p=0.016). Carriers of the A allele in the control group increased the risk of severe chronic periodontitis by 2.4 times compared to carriers of the G allele (OR=2.41; 95% CI 1.19-4.87; p=0.014). During the dental examination of employees of the ethylene oxide plant, the clinical course of periodontal diseases was more severe in comparison with the control group, and the number of patients with severe periodontitis was twice as high. It was found that the AA/AG genotypes of the IL-17A gene and the carrier of the A allele are associated with increased susceptibility to the development of severe chronic periodontitis. The association between the MMP-1 gene polymorphism and the risk of severe forms of chronic periodontitis has not been established. A risk factor for the development of inflammatory periodontal diseases in employees of the petrochemical complex is a complex of harmful production factors.

Contribution of Matrix Metalloproteinase-9 rs3918242 Genotypes to Childhood Leukemia Risk.

A single study has shown positive association and genotype-phenotype correlation between metalloproteinase-9 (MMP-9) promoter genotypes and adult acute lymphocytic leukemia (ALL). However, there is no report about childhood ALL. Thus, this study aimed at examining the role of MMP-9 rs3918242 genotypes in childhood ALL risk. A total of 266 childhood ALL cases and 266 healthy controls in Taiwan were examined for their MMP-9 rs3918242 genotypes via polymerase chain reaction-restriction fragment length polymorphism methodology. The MMP-9 rs3918242 CT or TT genotype carriers only had a slightly increased risk compared with CC carriers (p=0.6386 and 0.6005, respectively). The allelic frequency analysis also supported the idea that the variant T allele at MMP-9 rs3918242 is not differentially distributed between the case and control groups (p=0.4834). MMP-9 rs3918242 genotypes may indirectly influence the risk of childhood ALL. Further validations in other populations and analysis of the detail mechanisms are needed.

Genetic Polymorphisms of MMP1, MMP9, COL1A1, and COL1A2 in Polish Patients with Thoracic Aortopathy.

Background The pathogenesis of thoracic aortopathy is complex, and much evidence suggests the influence of genetic factors. Some genes with polymorphisms are widely considered critical factors in the initiation and development of aortic aneurysm. The aim of our study was to analyze the association of genetic polymorphisms of MMP1 rs1799750 (c.-1607G>GG), MMP9 rs3918242 (c.-1562C>T), COL1A1 rs1800012 (c.1245G>T), and COL1A2 rs42524 (c.1645G>C) with predisposition to thoracic aortopathy in Polish patients and with clinical characteristics of these patients. Methods The study was carried out with 96 patients with thoracic aortopathy (47 patients with ascending aortic aneurysm and 49 patients with thoracic aortic dissection) and 61 control subjects without thoracic aortopathy. The MMP1, MMP9, COL1A1, and COL1A2 polymorphisms were determined by PCR-RFLP. Results No significant differences in the frequency distributions of MMP1, MMP9, COL1A1, and COL1A2 genotypes or alleles were found (1) between the control group and patients with ascending aortic aneurysm (AsAA), (2) between the control group and patients with thoracic aortic dissection (TAD), or (3) between AsAA and TAD patients. Multivariate logistic regression analysis revealed that MMP1 and MMP9 polymorphisms were associated with the degree of aortic valve regurgitation. Conclusion The results of our study did not support associations between MMP1, MMP9, COL1A1, and COL1A2 genetic variants with the risk of thoracic artery disease in Polish patients. However, rs1799750 MMP1 and rs3918242 MMP9 seem to be associated with the degree of aortic regurgitation.

The Contribution of MMP-9 Genotypes to Pterygium in Taiwan.

The studies about the roles of matrix metalloproteinases (MMPs) in pterygium diagnosis and/or prognosis are mainly based on their mRNA and protein levels, while the genomic roles of MMPs are seldom examined. The aim of this study was to investigate the contribution of MMP-9 genotypes to pterygium risk. MMP-9 rs3918242 was genotyped in 134 pterygium cases and 268 controls via polymerase chain reaction-restriction fragment length polymorphism. The rs3918242 genotype percentages of CC, CT, and TT were 73.1, 25.4 and 1.5% among cases and 74.6, 23.1 and 2.3% among controls (p trend=0.7928). The odds ratios after adjusting for age and gender for CT and TT genotypes at rs3918242 were 1.08 and 0.92 (95%CI=0.66-1.73 and 0.45-2.89, p=0.6478 and 0.6389), respectively. In addition, allelic frequency analysis showed no significant difference in the distribution of allelic frequencies between the pterygium and control groups. The genotypes at MMP-9 rs3918242 play a minor role in determining personal susceptibility to pterygium.

A role of single nucleotide polymorphism in TNF, NOS3 and MMP9 genes at the risk of developing neonatal pneumonia

Neonatal pneumonia is one of the most common causes of infant mortality. Moreover, the diagnosis of this pathology represents a difficult task and requires to seek for additional solutions in clinical and laboratory practice. One of the current and promising ways to diagnose rerlies on search of predictive markers among the innate and adaptive immunity genes involved in disease pathogenesis. We used bioinformatics analysis to select genes playing essential role developing neonatal pneumonia. Next, cord blood samples collected from 234 newborns were examined by real-time polymerase chain reaction for nine polymorphic markers in the TNF, IL10, IL17A, IL17F, IL6, NOS3, and MMP9 genes. The results of statistical analysis showed that heterozygous genotypes in the MMP9 and TNF genes were associated with the risk of developing early neonatal pneumonia, and also the protective role of homozygotes AA in the MMP9 gene and GG in the TNF gene. A search for associations with a risk of intrauterine pneumonia revealed an unfavorable role for heterozygous genotypes in the NOS3 and MMP9 genes. Thus, due to difficulties in diagnosis or in case of developing neonatal pneumonia, it may be recommended to add genetic analysis for assessing polymorphic markers in the MMP9 (rs17576), TNF (rs1800629) and NOS3 (rs1549758) genes along with standard test assays.

Matrix Metalloproteinase Genes (MMP1, MMP10, MMP12) on Chromosome 11q22 and the Risk of Non-Contact Anterior Cruciate Ligament Ruptures.

Background: Sequence variants within the matrix metalloproteinases genes remain plausible biological candidates for further investigation of anterior cruciate ligament (ACL) rupture risk. The aim of the present study was to establish whether variants within the MMP1 (rs1799750, ->G), MMP10 (rs486055, C > T) and MMP12 (rs2276109, T > C) genes were associated with non-contact ACL rupture in a Polish cohort. Methods: The unrelated, self-reported Polish Caucasian participants consisted of 228 (157 male) individuals with primary non-contact ACL rupture and 202 (117 male) participants without any history of ACL rupture. All samples were genotyped in duplicate using the Applied Biosystems TaqMan® methodology. The statistical analyses were involved in determining the distribution of genotype and allele frequencies for the investigated polymorphisms between the diagnostic groups. Furthermore, pseudo-haplotypes were constructed to assess possible gene–gene interactions. Results: All genotype frequencies in the ACL rupture and control groups conformed to Hardy Weinberg Equilibrium expectations. None of the polymorphisms were associated with risk of non-contact ACL rupture under the codominant, dominant, recessive and over-dominant genetic models. Likewise, no genotype–genotype combinations inferred as “haplotypes” as a proxy of gene–gene interactions were associated with the risk of non-contact ACL ruptures. Conclusions: Despite the fact that the current study did not support existing evidence suggesting that variants within the MMP1, MMP10, and MMP12 genes influence non-contact ACL rupture risk, future work should include high-throughput sequencing technologies to identify potential targeted polymorphisms to fully characterize the 11q22 region with susceptibility to non-contact ACL rupture susceptibility in a Polish cohort.

Matrix metalloproteinases 9 and 14 polymorphisms and long-term complications in surgically treated breast cancer patients.

e24074 Background: Matrix metalloproteinases (MMPs) are zinc-containing endopeptidases that are involved in tissue remodeling. They can regulate interactions of cells with extracellular matrix and can play a role in wound healing. High levels of metalloproteinases have been correlated with significantly delayed wound healing in wounds of a variety of etiologies. The aim of our present study was to evaluate the association of MMP9 and MMP14 genetic polymorphisms with long-term complications of surgical treatment in breast cancer patients. Methods: The study included 99 breast cancer patients treated with either 75 or 37.5 mg of tramadol for pain relief after axillary breast cancer surgery as part of a randomized clinical trial KCT 04/2015-DORETAonko/si at Institute of Oncology Ljubljana. All patients were genotyped for MMP9 polymorphisms rs2250889, rs17577, rs17576, and rs20544 as well as MMP14 rs1042703, rs1042704, and rs743257. The association of genetic factors with long-term complications was evaluated using logistic regression. Results: One year after surgery, 24 (24.2%) patients had lymphedema, 25 (25.3%) experienced neuropathic pain and 21 (21.1%) experienced chronic pain. Carriers of polymorphic MMP9 rs2250889 allele experienced significantly more lymphedema compared to carriers of two wild-type alleles (OR = 3.45, 95% CI = 1.10-10.84, P = 0.034), even after adjustment for tramadol dose (OR = 3.76, 95% CI = 1.16-12.18, P = 0.027). Carriers of polymorphic MMP14 rs1042704 allele experienced more neuropathic pain compared to carriers of two wild-type alleles (OR = 3.21, 95% CI = 1.26-8.20, P = 0.015), even after adjustment for tramadol dose (OR = 3.80, 95% CI = 1.42-10.17, P = 0.008). Conclusions: MMP genetic variability was associated with long-term complications after axillary surgery in breast cancer patients, suggesting that MMPs may have an important role as modulators of wound healing.

Association of the polymorphisms of the genes APOC3 (rs2854116), ESR2 (rs3020450), HFE (rs1799945), MMP1 (rs1799750) and PPARG (rs1801282) with lipodystrophy in people living with HIV on antiretroviral therapy: a systematic review.

The aim of this study was to perform a systematic review to identify data reported in the literature concerning the association of APOC3 (rs2854116), ESR2 (rs3020450), HFE (rs1799945), MMP1 (rs1799750) and PPARG (rs1801282) polymorphisms with lipodystrophy in people living with HIV (PLWHIV) on antirretroviral therapy. The research was conducted in six databases and the studies were selected in two steps. First, a search was undertaken in the following electronic databases: PubMed, Science Direct, Medline, World Wide Science, Directory of Open Access Journals, Scielo, Lilacs and Medcarib. The titles and abstracts of 24,859 articles were read to select those that match the elegibilty criteria. Five papers that addressed the association of HAART, lipodystrophy and polymorphisms were selected for the review. There was no association between the polymorphisms of the genes APOC3 and PPARG and lipodystrophy. Another study described an association between the variant allele (G) of HFE and protection concerning the development of lipoatrophy (0.02) when compared with the reference allele (C). On the other hand, the variant allele (T) of the ESR2 gene was associated with the development of lipoatrophy (p = 0.007) when compared with the reference allele (C). In addition, the genotype and the variant allele of the gene MMP1 (2G) were associated with lipodystrophy in PLWHIV on HAART (p = 0.0002 and p = 0.0008, respectively). Therefore, further studies with other populations, involving PLWHIV on HAART are necessary to better understand the role of genetic markers, which may be involved in a predisposition to lipodystrophy.

Association Between MMP8 Gene Polymorphisms and Laryngeal Squamous Cell Carcinoma.

Matrix metalloproteinases (MMPs) are a family of proteins which are involved in breakdown of the extracellular matrix in embryonic development, tissue remodeling and in some diseases. MMP8 has both cancer-promoting and anticancer properties. However, the contribution of MMP8 to laryngeal squamous cell carcinoma (LSCC) has not been elucidated. In this study we aimed to test the contribution of two MMP8 polymorphisms, located in the gene promoter region, to the development of LSCC. This case-control study involved 569 DNA samples which were genotyped for two single nucleotide polymorphisms using real-time polymerase chain reaction method. Statistical analysis was performed with SPSS Statistics 20 software. Regression analysis adjusted by age showed that for MMP8 rs11225395 each minor A allele copy significantly reduced the odds for LSCC development (odds ratio=0.49, 95% confidence intervaI=0.04-2.19, p=0.048). MMP8 rs11225395 AA genotype was associated with smaller laryngeal tumour size (p=0.023). Smoking habit also correlated with laryngeal tumor size. MMP8 rs11225395 and smoking habits have a prominent interface with LSCC tumour size.

Investigation of MMP-9 rs3918242 and TIMP-2 rs8179090 polymorphisms in renal cell carcinoma tissues

Abstract Background The proteolytic activities of matrix metalloproteinases (MMP), cell surface enzymes degrading extracellular matrix, is inhibited by matrix metalloproteinase tissue inhibitors (TIMP). We aim to detect the effects of MMP-9 rs3918242 and TIMP-2 rs8179090 gene variations in renal cell cancer transformation. Methods One hundred tumor and 100 adjacent healthy tissues were obtained from the patients with renal cell cancer. Polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) was performed and the products carried out in agarose gel electrophoresis were visualized under UV light. Statistical analyses were performed using SPSS 22 and p-values of less than 0.05 were considered as statistically significant. Results MMP-9 rs3918242 T allele was higher in tumor tissues (36.5%) than adjacent tissues (17%) and odds ratio was found 2.8 in T allele (p&lt;0.001). Odds ratio values were found 3.325 in the carriers of TT genotype and 3.5 in the carriers of CT genotype compared to the carriers of CC genotype (p&lt;0.01). The polymorphism of TIMP-2 rs8179090 was not found statically significant in tumor and adjacent tissues (p&gt;0.05). Conclusion MMP-9 rs3918242 T allele, TT and CT genotypes can be used as biomarkers in determining of renal cell carcinoma.

Gene variability in matrix metalloproteinases in patients with recurrent aphthous stomatitis.

The development of recurrent aphthous stomatitis (RAS), inflammatory disease of oral mucosa, is influenced by both environmental and genetic factors. The aim of this study was to investigate polymorphisms located in seven genes coding different types of matrix metalloproteinases (MMPs)-collagenases (MMP1, MMP8, and MMP13), gelatinases (MMP2 and MMP9), stromelysin (MMP3), and membrane-type metalloproteinase (MMP16) in patients with RAS and healthy controls. Totally, 223 subjects were included in this case-control study and their detailed anamnestic, clinical, and laboratory parameters were recorded. Seventy-seven patients with RAS and 146 controls were genotyped for seventeen polymorphisms in the MMPs genes using the real-time polymerase chain reaction (PCR) or PCR with restriction analysis. Allele, genotype, and haplotype frequencies of the studied polymorphisms between RAS patients and controls were similar, except for allele distributions of MMP1 rs1144393, MMP9 rs3918242, and MMP16 rs10429371, which were different between patients with RAS and healthy controls (P=.023, P=.049 and P=.025, all Pcorr >0.05, respectively). Moreover, the comparison of genotype frequencies (TT vs CC+CT) of the MMP16 rs10429371 variant showed a marginally significant difference between RAS patients and controls (P=.05, Pcorr >0.05, OR=1.68, 95% CI=0.95-2.98). No significant relationship between investigated polymorphisms in seven MMPs genes and RAS development in the Czech population was observed in this study.

Association of MMP-2, MMP-3, and MMP-9 Polymorphisms with Susceptibility to Recurrent Pregnancy Loss

Background Genetic causes that contribute to recurrent pregnancy loss (RPL) are not fully understood. The aim of this study was to evaluate the association of five polymorphisms at MMP-2, MMP-3, and MMP-9 genes with risk of RPL. Methods: The study comprised 250 women with RPL and 250 healthy controls. The MMP-2 (rs243865, rs2285053), MMP-3 (rs35068180), and MMP 9 (rs3918242, rs17576) polymorphisms were genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay. Results: A significant association was found between MMP-3 rs35068180 polymorphism and RPL risk. There was no significant association between RPL and polymorphisms at MMP-2 (rs243865, rs2285053) and MMP 9 (rs3918242, rs17576) genes. Conclusion: MMP-3 rs35068180 polymorphism may modulate RPL risk in Iranian women. There is no evidence to suggest that MMP-2 (rs243865, rs2285053) and MMP 9 (rs3918242, rs17576) polymorphisms are associated with RPL risk.