scholarly journals Polymorphism of MMP-3 gene and imbalance expression of MMP-3 / TIMP-1 in articular cartilage are associated with an endemic osteochondropathy, Kashin- Beck disease

2022 ◽  
Vol 23 (1) ◽  
Author(s):  
Bohui Shi ◽  
Xiong Guo ◽  
Aili Iv ◽  
Zengtie Zhang ◽  
Xiaowei Shi

Abstract Background The etiology of Kashin-Beck disease (KBD), an endemic osteochondropathy, is largely unknown. Matrix metalloproteinase-3 (MMP-3) plays a central role in the initiation and progression of cartilage destruction, however, no study has reported on the relationship between KBD and MMP-3. The objective of this study was to explore the polymorphism of MMP-3 gene and expression of MMP-3 / TIMP-1(Tissue inhibitors of matrixmetalloproteinases-1) in the pathogenesis of KBD. Methods Single nucleotide polymorphism (SNP) genotyping was conducted in 274 KBD cases and 248 healthy controls for eight SNPs in MMP-3 using the Sequenom MassARRAY system. Additionally, the expression of MMP-3、TIMP-1 in different layers of the articular cartilage was analyzed by immunohistochemistry for 22 KBD patients, 15 osteoarthritis (OA) patients and 21 controls. Results The results showed that six SNPs (rs520540、rs591058、rs679620、rs602128、rs639752 and rs678815) in MMP-3 were associated with the increased risk of KBD, however, after Bonferroni correction, only the SNP rs679620 in the recessive model remained significant difference (OR = 2.31, 95%CI = 1.29–4.14, P = 0.0039), homozygous for “T” allele have a risk for KBD than “C” allele carriers. Moreover, the percentages of cells expressing MMP-3 in articular cartilage were significantly higher in the KBD and OA groups than in the controls (t = 5.37 and 4.19, P<0.01). While the KBD and OA groups had lower levels of TIMP-1 positive staining compared with the controls (t = 5.23and 5.06, P<0.01). And there was no significant different between KBD and OA for the levels of MMP-3 and TIMP-1 positive staining (t = 0.05and 0.28, P>0.05). Conclusions MMP-3 is associated with the susceptibility of KBD, and the imbalance expression of MMPs / TIMPs leading to cartilage degradation may play an important role in cartilage degradation and osteoarthritis formation in OA and KBD.

2021 ◽  
Author(s):  
Bohui Shi ◽  
Xiong Guo ◽  
Aili lv ◽  
Zengtie Zhang ◽  
Xiaowei Shi

Abstract Background: The etiology of Kashin-Beck disease (KBD), an endemic osteochondropathy, is largely unknown. Matrix metalloproteinase-3 (MMP-3) plays a central role in the initiation and progression of cartilage destruction, however,no study has reported on the relationship between KBD and MMP-3. The objective of this study was to explore the polymorphism of MMP-3 gene and expression of MMP-3 / TIMP-1(Tissue inhibitors of matrixmetalloproteinases-1) in the pathogenesis of KBD.Methods: Single nucleotide polymorphism (SNP) genotyping was conducted in 274 KBD cases and 248 healthy controls for eight SNPs in MMP-3 using the Sequenom MassARRAY system. Additionally, the expression of MMP-3、TIMP-1 in different layers of the articular cartilage was analyzed by immunohistochemistry for 22 KBD patients, 15 osteoarthritis (OA) patients and 21 controls.Results: The results showed that six SNPs (rs520540、rs591058、rs679620、rs602128、rs639752 and rs678815) in MMP-3 were associated with the increased risk of KBD, however, after Bonferroni correction, only the SNP rs679620 in the recessive model remained significant difference (OR=2.31, 95%CI=1.29-4.14, P=0.0039), homozygous for “T” allele have a risk for KBD than "C" allele carriers. Moreover, the percentages of cells expressing MMP-3 in articular cartilage were significantly higher in the KBD and OA groups than in the controls (t=5.37 and 4.19,P<0.01).While the KBD and OA groups had lower levels of TIMP-1 positive staining compared with the controls (t=5.23and 5.06,P<0.01). And there was no significant different between KBD and OA for the levels of MMP-3 and TIMP-1 positive staining (t=0.05and 0.28,P>0.05). Conclusions: MMP-3 is associated with the susceptibility of KBD, and the imbalance expression of MMPs / TIMPs leading to cartilage degradation may play an important role in cartilage degradation and osteoarthritis formation in OA and KBD.


2021 ◽  
Vol 10 (15) ◽  
pp. 3309
Author(s):  
Gisella Gennaro ◽  
Melissa L. Hill ◽  
Elisabetta Bezzon ◽  
Francesca Caumo

Contrast-enhanced mammography (CEM) demonstrates a potential role in personalized screening models, in particular for women at increased risk and women with dense breasts. In this study, volumetric breast density (VBD) measured in CEM images was compared with VBD obtained from digital mammography (DM) or tomosynthesis (DBT) images. A total of 150 women who underwent CEM between March 2019 and December 2020, having at least a DM/DBT study performed before/after CEM, were included. Low-energy CEM (LE-CEM) and DM/DBT images were processed with automatic software to obtain the VBD. VBDs from the paired datasets were compared by Wilcoxon tests. A multivariate regression model was applied to analyze the relationship between VBD differences and multiple independent variables certainly or potentially affecting VBD. Median VBD was comparable for LE-CEM and DM/DBT (12.73% vs. 12.39%), not evidencing any statistically significant difference (p = 0.5855). VBD differences between LE-CEM and DM were associated with significant differences of glandular volume, breast thickness, compression force and pressure, contact area, and nipple-to-posterior-edge distance, i.e., variables reflecting differences in breast positioning (coefficient of determination 0.6023; multiple correlation coefficient 0.7761). Volumetric breast density was obtained from low-energy contrast-enhanced spectral mammography and was not significantly different from volumetric breast density measured from standard mammograms.


2021 ◽  
Vol In Press (In Press) ◽  
Author(s):  
Maryam Saneipour ◽  
Abdolkarim Sheikhi ◽  
Abbas Moridnia

Background: Breast cancer (BC) is the most common malignant tumor in women around the world. Genetic factors do play a vital role in the development and progression of BC. Genetic alterations in the ESR1 (estrogen receptor 1) gene can lead to estrogen dysfunction and increased risk for BC. Nevertheless, due to genetic diversity, the information from different studies is contradictory and controversial. Objectives: This study aimed to investigate the potential relationship between the rs1801132 and rs2234693 single nucleotide polymorphism (SNPs) of the ESR1 gene with susceptibility to BC in the Iranian population. Methods: The genotyping of the rs2234693 and rs1801132 SNPs was assessed in 63 BC patients referred to Imam Hasan Mojtaba Center, which is a charity-based foundation for cancer care in Dezful, Iran, from March 2018 to November 2019. Also, 65 healthy women were selected as a control group. The genotyping of the SNPs was performed using the high-resolution melting (HRM) technique and confirmed by DNA sequencing. Results: The genotype distribution and allele frequency of the rs2234693 SNP were significantly different in BC patients compared to the control group (genotype frequency with P = 0.018 and allele frequency with P = 0.004, OR = 2.085, 95% CI = 1.253 -3.468). In genetic models, rs2234693 increased BC risk in recessive model (P = 0.005, OR = 2.813, 95% CI = 1.363 - 5.802). However, there was no significant difference regarding genotype distribution of the rs1801132 SNP between the BC patients and controls. Conclusions: Our results showed that the CC genotype of the rs2234693 SNP is significantly associated with BC. Accordingly, it can be suggested that the rs2234693 SNP be considered for susceptibility to BC.


Author(s):  
Chandan K. Jha ◽  
Rashid Mir ◽  
Imadeldin Elfaki ◽  
Naina Khullar ◽  
Suriya Rehman ◽  
...  

Aim: Studies have evaluated the association of miRNA-423 C>A genotyping with the susceptibility to various diseases such cancers, atherosclerosis and inflammatory bowel disease but the results were contradictory. However, no studies have reported the association between miRNA-423 rs6505162 C>A polymorphism and susceptibility of coronary artery disease. MicroRNAs regulate expression of multiple genes involved in atherogenesis. Therefore, we investigated the association of microRNA-423C>T gene variations with susceptibility to coronary artery disease. Methodology: This study was conducted on 100 coronary artery disease patients and 117 matched healthy controls. The genotyping of the microRNA-423 rs6505162C>A was performed by using Amplification refractory mutation system PCR method (ARMS-PCR). Results: A significant difference was observed in the genotype distribution among the coronary artery disease cases and sex-matched healthy controls (P=0.048). The frequencies of all three genotypes CC, CA, AA reported in the patient’s samples were 55%, 41% and 4% and in the healthy controls samples were 55%, 41% and 4% respectively. Our findings showed that the microRNA-423 C>A variant was associated with an increased risk of coronary artery disease in codominant model (OR = 1.96, 95 % CI, 1.12-3.42; RR 1.35(1.05-1.75, p=0.017) of microRNA-423CA genotype and significant association in dominant model (OR 1.97, 95% CI (1.14-3.39), (CA+AA vs CC) and non-significant association for recessive model (OR=1.42, 95%CI=0.42-4.83, P=0.56, AA vs CC+CA).While, the A allele significantly increased the risk of coronary artery disease (OR =1.56, 95 % CI, 1.03-2.37; p=0.035) compared to C allele. Therefore, it was observed that more than 1.96, 1.97 and 1.56 fold increased risk of developing coronary artery disease. Conclusion: Our findings indicated that microRNA-423 CA genotype and A allele are associated with an increased susceptibility to Coronary artery disease.


2016 ◽  
Vol 6 (2) ◽  
pp. 80-87
Author(s):  
Mohammed Momenuzzaman Khan ◽  
Md Nazmul Huda ◽  
Manabendra Bhattacharjee ◽  
Md Jalal Uddin ◽  
Mustofa Kamal Uddin Khan

Background: Migraine is an important cause of headache and headache-related disabilities. It increases loss of working time, causes inability to carry out daily activities and disruption of family and social life. The pathophysiology of migraine is still poorly understood. On the other hand, the prevalence of obesity is constantly increasing worldwide. The consequence of overweight and obesity includes increased risk of diabetes mellitus, dyslipidemia, hypertension, cardiovascular disease and cancer.Objectives: This study was performed to assess the relationship between BMI and migraine by finding out the relationship between migraine frequency and duration in different BMI groups, comparing the socio-demographic variables in migraine and non-migraine patients and to find out the migraine related co-morbidities.Materials and Methods: This observational case-control study was conducted on 100 subjects aged 12–50 years in the Neurology Outpatient Department, Mymensingh Medical College Hospital, Mymensingh in the period of January 2011 to December 2012. Out of total subjects fifty migraine patients were selected as cases and fifty nonmigraineurs as controls. Subjects were then categorized in three groups based on BMI: <23, 23 to 25 and >25. Collected data were compiled and appropriate analyses were done by using computer based software, Statistical Package for Social Sciences (SPSS) version 16.0. For statistical analysis one way ANOVA tests were done for comparing means of quantitative data and Chi-square tests were done for qualitative data. A p value <0.05 was considered statistically significant.Results: In this study, majority (>95%) of the study subjects were between 10 and 35 years of age. Mean age of case group was found 25.55 ± 5.87 and that of control was 25.53 ± 4.22 years. Case group contained 10 (20%) males and 40 (80%) females whereas control group had 14 (28%) males and 36 (72%) females. Number of female cases and controls were higher than that of male. In control group 30 (60%) were unmarried and 20 (40%) were married. There was no significant difference in the financial condition between case and control groups. Students and housewives occupied the largest number of study subjects who were unemployed. Regarding residence, rural and urban patients were equal in case group and in control group 29 (58%) were urban and 21 (42%) rural. Mean duration of headache was 8.9 ± 7.5, 5.8 ± 6.7, 9.6 ± 14.3 years in different BMI groups (<23, 23–25, >25 respectively) in case group and 4.6 ± 5.3, 4.4 ± 3.4, 3.4 ± 1.4 years in control group respectively. There was significant difference in quality of headache. In migrainous group 58.6% in BMI <23, 30% in BMI 23–25, 36.4% in BMI >25 noted their headache as throbbing, in contrast most of the nonmigrainous described them as dull in nature. Mean frequency of headache per month was significantly higher in migraine group compared to non-migraine group (p=0.02). Regarding associated symptoms, nausea, vomiting, photophobia and phonophobia were observed significantly higher in migraine patients in BMI <23 group. Odd ratios (ORs) for vomiting, photophobia and phonophobia with 95% confidence interval (CI) were 23.385 (2.752–97.739), 16.500 (3.060– 88.971) and 13.000 (2.922–57.846) respectively. Smoking was found significantly higher in nonmigrainous group than migraine group in case of BMI <23.Conclusion: From the result of present study it can be concluded that there is statistically no significant relation of BMI with frequency of headache, but some relationship were observed for associated symptoms of migraine with low BMI.J Enam Med Col 2016; 6(2): 80-87


2019 ◽  
Vol 39 (5) ◽  
Author(s):  
Cheng Tan ◽  
Junzhi Liu ◽  
Jun Wei ◽  
Shoujun Yang

Abstract Background : Several studies investigated the relationship between antisense non-coding RNA in the INK4 locus (ANRIL) variants and the risk of ischemic stroke (IS), yet whether ANRIL variants are associated with IS remain controversial. Therefore, we performed the present study to obtain a more conclusive result. Methods: Literature retrieval was conducted in PubMed, Medline and Embase. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated. Results: Eighteen studies were enrolled for analyses. Pooled overall analyses showed that rs2383206 (recessive model: P=0.002, OR = 1.22, 95%CI 1.08–1.38; allele model: P=0.003, OR = 0.90, 95%CI 0.84–0.96) and rs10757274 (allele model: P=0.006, OR = 0.91, 95%CI 0.86–0.97) variants were significantly associated with an increased risk of IS. Further subgroup analyses by ethnicity revealed that rs2383206, rs10757274 and rs10757278 variants were all significantly correlated with an increased risk of IS in Asians. Additionally, rs10757278 polymorphism was also significantly correlated with an increased risk of IS in Caucasians. Conclusions: Our findings indicated that rs2383206, rs10757274 and rs10757278 variants may impact individual susceptibility to IS in Asians. Moreover, rs10757278 polymorphism may also impact individual susceptibility to IS in Caucasians.


2015 ◽  
Vol 5 (1) ◽  
Author(s):  
Jie Yan ◽  
Xiantao Wang ◽  
Hui Tao ◽  
Zengfu Deng ◽  
Wang Yang ◽  
...  

Abstract Prostate cancer is one of the most common noncutaneous malignancies in Western countries. Because there has been a debate regarding the relationship between the XRCC1-Arg399Gln and Arg280His polymorphisms and prostate cancer risk, we therefore performed this meta-analysis. The electronic databases PubMed, EMBASE and Medline were searched prior to October 1, 2014. An odds ratio and 95% confidence interval were used to calculate association. Heterogeneity was tested by both a chi-square test and I2statistic. Funnel plots and Egger’s test were used to assess publication bias. All statistical analyses were performed using STATA 12.0 software. A significant association between the XRCC1-Arg399Gln polymorphism and prostate cancer risk was found under a homozygote model and a recessive model. A significant association between XRCC1-Arg280His and prostate cancer risk was found under a heterozygote model and a dominant model. Overall, the results of this meta-analysis show that the XRCC1-Arg399Gln polymorphism may be associated with an increased risk for prostate cancer under the homozygote model and the recessive model. And XRCC1-Arg280His polymorphism is likely to be related with prostate cancer risk under the heterozygote model and the dominant model. Additional larger well-designed studies are needed to validate our results.


2021 ◽  
Author(s):  
Tingting Liu ◽  
Yuju Cao ◽  
Changxu Han ◽  
Feimeng An ◽  
Tiantian Wang ◽  
...  

Abstract IntroductionSteroid-induced osteonecrosis of the femoral head (ONFH ) is a disease of bone metabolism, and genetic factors are generally considered to play an important role. The purpose of this study was to investigate the relationship between single nucleotide polymorphisms (SNPs) in MIR17HG and MIR155HG and the risk of steroid-induced ONFH in the population of northern China.MethodsA total of 199 steroid-induced ONFH patients and 506 healthy controls were recruited for the study. Four SNPs of MIR17HG and seven SNPs of MIR155HG were genotyped by Sequenom MassARRAY. ORs and 95% CIs were used to evaluate the relationship between these SNPs and steroid-induced ONFH.ResultsIn the codominant model, patients with the MIR17HG SNPs(rs7318578) AA genotype had an increased risk of steroid-induced ONFH (OR = 1.79, p = 0.039), in the recessive model, patients with the MIR17HG SNP(rs7318578) AA genotype had an increased risk of steroid-induced ONFH (OR = 1.78, p = 0.032). Stratified analysis showed that a MIR17HG SNP (rs7318578) and MIR155HG SNPs(rs77218221, rs11911469, rs34904192 and rs4143370) were closely related to different unornamented phenotypes of steroid-induced ONFH. Analysis of the clinical indicators revealed significant differences in high-density lipoprotein (HDL-C) levels between the ONFH group and the control group (p = 0.005). MIR17HG SNP(rs75267932) and MIR155HG SNPs(rs77699734, rs1893650 and rs34904192) were correlated with different lipid indexes.ConclusionOur results confirm that MIR17HG and MIR155HG gene mutations are associated with steroid-induced ONFH susceptibility in the population of northern China, providing new evidence for the early detection and prevention of ONFH.


2020 ◽  
Vol 26 (5) ◽  
pp. 398-402
Author(s):  
Haibo Ge ◽  
Shi Chen ◽  
Jia Zhu

This meta-analysis was conducted to assess the consistency and strength of the relationship between polymorphism of IL-2 -330T/G and susceptibility to pulmonary tuberculosis (TB). PubMed, Web of Knowledge and CNKI were searched to find eligible studies about the relationship between IL-2 -330T/G polymorphism and susceptibility to pulmonary TB. A total of eight studies comprising 971 cases and 1519 controls were grouped together for the purpose of elucidating the relationship between polymorphism of IL-2 -330T/G and pulmonary TB susceptibility. The allele model (G vs. T: odds ratio (OR) = 1.34; 95% confidence interval (CI) 1.05–1.71, Phet = 0.001) and the recessive model (GG+GT vs. TT: OR = 1.60; 95% CI 1.08–2.38, Phet = 0.0001) showed an increased risk of development of pulmonary TB. However, the homozygous model (GG vs. TT: OR = 1.74; 95% CI 0.98–3.09, Phet = 0.0005) and the dominant model (GG vs. TT + TG: OR = 1.30; 95% CI = 0.80-2.14, Phet =  0.001) failed to show an increased incidence of pulmonary TB. When analysis was stratified by ethnicity, no obvious associations were identified in the Caucasian subgroup under all four genetic models. Additionally, heterogeneity disappeared in the analysis of Caucasian subgroup. Our combined data suggested that there was no association between IL-2 -330T/G polymorphism and pulmonary TB among Caucasians.


2020 ◽  
pp. 1098612X2097779
Author(s):  
Siti M Zainal Ariffin ◽  
David Bennett ◽  
William R Ferrell ◽  
John C Lockhart ◽  
Lynette Dunning ◽  
...  

Objectives The aim of this study was to determine the presence of protease-activated receptor 2 (PAR2) and matriptase proteins and quantify PAR2 and matriptase mRNA expression in the articular cartilage and synovial membrane of cats with and without osteoarthritis (OA). Methods A total of 28 articular cartilage samples from adult cats (14 OA and 14 normal), 10 synovial membranes from adult cats (five OA and five normal) and three cartilage samples from 9-week-old fetal cats were used. The presence of PAR2 and matriptase in the cartilage and synovial membrane of the adult samples was detected by immunohistochemical (IHC) staining, while real-time PCR was used for mRNA expression analyses in all samples. Results PAR2 was detected in all OA and normal articular cartilage and synovial membrane samples but confined to only a few superficial chondrocytes in the normal samples. Matriptase was only detected in OA articular cartilage and synovial membrane samples. PAR2 and matriptase mRNA expression were, however, detected in all cartilage and synovial membrane samples. PAR2 and matriptase mRNA expression levels in OA articular cartilage were five ( P <0.001) and 3.3 ( P <0.001) times higher than that of the healthy group, respectively. There was no significant difference ( P = 0.05) in the OA synovial membrane PAR2 and matriptase mRNA expression compared with the normal samples. Conclusions and relevance Detection of PAR2 and matriptase proteins and gene expression in feline articular tissues is a novel and important finding, and supports the hypothesis that serine proteases are involved in the pathogenesis of feline OA. The consistent presence of PAR2 and matriptase protein in the cytoplasm of OA chondrocytes suggests a possible involvement of proteases in cartilage degradation. Further investigations into the PAR2 and matriptase pathobiology could enhance our understanding of the proteolytic cascades in feline OA, which might lead to the development of novel therapeutic strategies.


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