scholarly journals Novel data about association of the functionally significant polymorphisms of the MMP-9 gene with exfoliation glaucoma in the Caucasian population of Central Russia

2020 ◽  
Author(s):  
Dina Starikova ◽  
Irina Ponomarenko ◽  
Evgeny Reshetnikov ◽  
Volodymyr Dvornyk ◽  
Mikhail Churnosov
Keyword(s):  
Regulatory Protein ◽  
Additive Model ◽  
Caucasian Population ◽  
Control Group ◽  
Regulatory Motifs ◽  
Exfoliation Glaucoma ◽  
Central Russia ◽  
Increased Risk ◽  
Evolutionarily Conserved

Aim: This study aimed to investigate the role of functionally significant polymorphisms of the MMP-1, MMP-3, and MMP-9 genes in the development of exfoliation glaucoma (XFG) in the Caucasian population of Central Russia. Methods: The study sample consisted of 724 participants, including 328 patients with XFG and 396 individuals in the control group. The participants were of Russian ethnicity (self-reported) born in Central Russia. The participants were genotyped at eight functionally significant polymorphisms of the MMP genes (rs3918242, rs3918249, rs17576, rs3787268, rs2250889, rs17577 MMP9, rs679620 MMP3, and rs1799750 MMP1). The association analysis was performed using logistic regression. Two polymorphisms, which were associated with XFG, and 12 polymorphisms linked to them (r2≥0.8) were analyzed for their functional significance in silico. Results: Allele C of rs3918249 MMP9 was associated with XFG according to the additive model (OR = 0.75, 95% CI 0.56-0.93, pperm = 0.015), and allele G of the rs2250889 MMP9 locus was associated with XFG according to the additive (OR = 1.59, 95% CI 1.10-2.29, pperm = 0.013) and dominant (OR = 1.68, 95% CI 1.11- 2.56, рperm = 0.016) models. Two XFG-associated loci of the MMP9 gene и 12 SNPs linked to them had a significant regulatory potential (they are located in the evolutionarily conserved regions, promoter and enhancer histone marks, the DNAase- hypersensitivity regions, a region binding to regulatory protein and a region of regulatory motifs) and may influence the expression of 13 genes and alternative splicing of four genes in various tissues and organs related to the pathogenesis of XFG. Conclusion: Allele C rs3918249 MMP9 decreased risk for XFG (OR = 0.75) and allele G of the rs2250889 MMP9 locus increased risk for XFG (OR = 1.59-1.68) in the Caucasian population of Central Russia.

scholarly journals Plasma Branched-Chain Amino Acids and Incident Cardiovascular Disease in the PREDIMED Trial

2016 ◽  
Vol 62 (4) ◽  
pp. 582-592 ◽  
Author(s):  
Miguel Ruiz-Canela ◽  
Estefania Toledo ◽  
Clary B Clish ◽  
Adela Hruby ◽  
Liming Liang ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Amino Acids ◽  
Cardiovascular Death ◽  
Branched Chain Amino Acids ◽  
Control Group ◽  
Cvd Risk ◽  
Hazard Ratios ◽  
Increased Risk ◽  
Branched Chain

Abstract BACKGROUND The role of branched-chain amino acids (BCAAs) in cardiovascular disease (CVD) remains poorly understood. We hypothesized that baseline BCAA concentrations predict future risk of CVD and that a Mediterranean diet (MedDiet) intervention may counteract this effect. METHODS We developed a case-cohort study within the Prevención con Dieta Mediterránea (PREDIMED), with 226 incident CVD cases and 744 noncases. We used LC-MS/MS to measure plasma BCAAs (leucine, isoleucine, and valine), both at baseline and after 1 year of follow-up. The primary outcome was a composite of incident stroke, myocardial infarction, or cardiovascular death. RESULTS After adjustment for potential confounders, baseline leucine and isoleucine concentrations were associated with higher CVD risk: the hazard ratios (HRs) for the highest vs lowest quartile were 1.70 (95% CI, 1.05–2.76) and 2.09 (1.27–3.44), respectively. Stronger associations were found for stroke. For both CVD and stroke, we found higher HRs across successive quartiles of BCAAs in the control group than in the MedDiet groups. With stroke as the outcome, a significant interaction (P = 0.009) between baseline BCAA score and intervention with MedDiet was observed. No significant effect of the intervention on 1-year changes in BCAAs or any association between 1-year changes in BCAAs and CVD were observed. CONCLUSIONS Higher concentrations of baseline BCAAs were associated with increased risk of CVD, especially stroke, in a high cardiovascular risk population. A Mediterranean-style diet had a negligible effect on 1-year changes in BCAAs, but it may counteract the harmful effects of BCAAs on stroke.

scholarly journals Evaluation of the Role of ABCB1gene Polymorphic Variants on Psychiatric Disorders Predisposition in Macedonian Population

PRILOZI ◽  
2017 ◽  
Vol 38 (3) ◽  
pp. 71-88
Author(s):  
Zorica Naumovska ◽  
Aleksandra K. Nestorovska ◽  
Zoran Sterjev ◽  
Ana Filipce ◽  
Aleksandra Grozdanova ◽  
...  
Keyword(s):  
Bipolar Disorder ◽  
Psychiatric Disorders ◽  
Psychiatric Illness ◽  
Cell Activation ◽  
Bipolar Disorders ◽  
Control Group ◽  
Microglia Cell ◽  
Increased Risk ◽  
And Function

Abstract The psychiatric and other CNS disorders are characterized with unregulated neuro-inflammatory processes and chronic microglia cell activation resulting with detrimental effect. ABCB1gene polymorphismsC1236T, G2677T/Aand C3435T are associated with P-glycoprotein expression and function andare linked with predisposition to psychiatric disorders such as schizophrenia and bipolar disorders. The relationship between mood disorders and glucocorticoids has been confirmed and ABCB1 SNPs influence the glucocorticoids access to the brain. The aim of the study is evaluation of the influence of the three most common ABCB1SNPs on predisposition to psychiatric disorders in Macedonian population. In the study 107 unrelated healthy Macedonians of both sexes were enrolled as a control group and patient population of 54 patients (22 to 65 years old) diagnosed with schizophrenia or bipolar disorder. ABCB1 for three polymorphisms were analyzed by Real-Time PCR in both groups. The results have confirmed the role of the ABCB1 gene in predisposition to psychiatric disorders and increased risk of developing bipolar disorder in carriers of the heterozygotes and mutant homozygotes for polymorphic variations in 1236 and 2677 in comparison to the normal genotype carriers. Three-fold higher risk was estimated for psychiatric illness in women that are 1236 and 2677 heterozygous carrier (heterozygous and mutant homozygous) compared to healthy control (men and women) population and four-fold higher risk in comparison only to healthy women population. Mutant allele carriers for 1236 and 2677 polymorphisms that are 35 years and below in patients population have almost three-fold higher risk for development of psychiatric illness.

scholarly journals ThechbGGene of the Chitobiose (chb) Operon of Escherichia coli Encodes a Chitooligosaccharide Deacetylase

2012 ◽  
Vol 194 (18) ◽  
pp. 4959-4971 ◽  
Author(s):  
Subhash Chandra Verma ◽  
Subramony Mahadevan
Keyword(s):  
Escherichia Coli ◽  
Metal Binding ◽  
Inflammatory Diseases ◽  
Regulatory Protein ◽  
Loss Of Function ◽  
Content Type ◽  
Reading Frame ◽  
E Coli ◽  
Evolutionarily Conserved

ABSTRACTThechboperon ofEscherichia coliis involved in the utilization of the β-glucosides chitobiose and cellobiose. The function ofchbG(ydjC), the sixth open reading frame of the operon that codes for an evolutionarily conserved protein is unknown. We show thatchbGencodes a monodeacetylase that is essential for growth on the acetylated chitooligosaccharides chitobiose and chitotriose but is dispensable for growth on cellobiose and chitosan dimer, the deacetylated form of chitobiose. The predicted active site of the enzyme was validated by demonstrating loss of function upon substitution of its putative metal-binding residues that are conserved across the YdjC family of proteins. We show that activation of thechbpromoter by the regulatory protein ChbR is dependent on ChbG, suggesting that deacetylation of chitobiose-6-P and chitotriose-6-P is necessary for their recognition by ChbR as inducers. Strains carrying mutations inchbRconferring the ability to grow on both cellobiose and chitobiose are independent ofchbGfunction for induction, suggesting that gain of function mutations in ChbR allow it to recognize the acetylated form of the oligosaccharides. ChbR-independent expression of the permease and phospho-β-glucosidase from a heterologous promoter did not support growth on both chitobiose and chitotriose in the absence ofchbG, suggesting an additional role ofchbGin the hydrolysis of chitooligosaccharides. The homologs ofchbGin metazoans have been implicated in development and inflammatory diseases of the intestine, indicating that understanding the function ofE. colichbGhas a broader significance.

Genetic variants of interferon-gamma and its mRNA expression and inflammatory parameters in the pathogenesis of vitiligo

2017 ◽  
Vol 95 (4) ◽  
pp. 474-481 ◽  
Author(s):  
Rehab A. Karam ◽  
Haidy E. Zidan ◽  
Mohamed H. Khater
Keyword(s):  
Elevated Serum ◽  
Serum Levels ◽  
Intercellular Adhesion Molecule ◽  
Control Group ◽  
Intercellular Adhesion Molecule 1 ◽  
Inflammatory Parameters ◽  
Increased Risk ◽  
Tnf Α ◽  
Ifn Γ

Although genetics plays an essential role in the pathogenesis of vitiligo, vitiligo pathogenesis is still unclear. Our aim was to investigate the role of IFN-γ expression and polymorphism in vitiligo susceptibility and whether intercellular adhesion molecule-1 (ICAM-1), tumor necrosis factor (TNF)-α, and TNF-β play a role in vitiligo pathogenesis as important inflammatory parameters. Eighty-five patients with vitiligo and 90 controls were investigated for IFN-γ gene expression by quantitative real-time PCR and genotyped for IFN-γ +874T/A (rs2430561) and IFN-γ +2109A/G (rs1861494) gene polymorphisms by sequence-specific primer (SSP)-PCR and PCR-restriction fragment length polymorphism (RFLP), respectively. Serum levels of inflammatory parameters were measured using ELISA. Frequencies of the +874 TT genotype and T allele were significantly higher in patients with active vitiligo than in stable patients (P = 0.01 and 0.03, respectively). Calculation of odds ratio suggested a 1.7-fold increased risk of vitiligo in individuals having the TA haplotype. We observed overexpression of IFN-γ mRNA with elevated serum levels of IFN-γ, ICAM-1, TNF-α, and TNF-β in patients with vitiligo when compared with the control group (P = 0.001, for all). In addition, these levels were elevated in patients with active vitiligo compared with stable patients with vitiligo (P = 0.008, 0.006, 0.01, 0.01, and 0.03, respectively), which suggests the involvement of these cytokines in disease activity. In conclusion, IFN-γ is a promising immunological marker in vitiligo pathogenesis.

scholarly journals The C-terminal dimerization motif of cyclase-associated protein is essential for actin monomer regulation

2016 ◽  
Vol 473 (23) ◽  
pp. 4427-4441 ◽  
Author(s):  
Shohei Iwase ◽  
Shoichiro Ono
Keyword(s):  
Regulatory Protein ◽  
Full Length ◽  
Regulatory Function ◽  
Actin Monomer ◽  
Nucleotide Exchange ◽  
Strong Activity ◽  
Filament Dynamics ◽  
Evolutionarily Conserved ◽  
Syndrome Protein

Cyclase-associated protein (CAP) is a conserved actin-regulatory protein that functions together with actin depolymerizing factor (ADF)/cofilin to enhance actin filament dynamics. CAP has multiple functional domains, and the function to regulate actin monomers is carried out by its C-terminal half containing a Wiskott–Aldrich Syndrome protein homology 2 (WH2) domain, a CAP and X-linked retinitis pigmentosa 2 (CARP) domain, and a dimerization motif. WH2 and CARP are implicated in binding to actin monomers and important for enhancing filament turnover. However, the role of the dimerization motif is unknown. Here, we investigated the function of the dimerization motif of CAS-2, a CAP isoform in the nematode Caenorhabditis elegans, in actin monomer regulation. CAS-2 promotes ATP-dependent recycling of ADF/cofilin-bound actin monomers for polymerization by enhancing exchange of actin-bound nucleotides. The C-terminal half of CAS-2 (CAS-2C) has nearly as strong activity as full-length CAS-2. Maltose-binding protein (MBP)-tagged CAS-2C is a dimer. However, MBP-CAS-2C with a truncation of either one or two C-terminal β-strands is monomeric. Truncations of the dimerization motif in MBP-CAS-2C nearly completely abolish its activity to sequester actin monomers from polymerization and enhance nucleotide exchange on actin monomers. As a result, these CAS-2C variants, also in the context of full-length CAS-2, fail to compete with ADF/cofilin to release actin monomers for polymerization. CAS-2C variants lacking the dimerization motif exhibit enhanced binding to actin filaments, which is mediated by WH2. Taken together, these results suggest that the evolutionarily conserved dimerization motif of CAP is essential for its C-terminal region to exert the actin monomer-specific regulatory function.

scholarly journals Monocyte-Derived Macrophages Are Impaired in Myelodysplastic Syndrome

2016 ◽  
Vol 2016 ◽  
pp. 1-7 ◽  
Author(s):  
Yu Han ◽  
Huaquan Wang ◽  
Zonghong Shao
Keyword(s):  
Myelodysplastic Syndrome ◽  
Ex Vivo ◽  
Regulatory Protein ◽  
Control Group ◽  
Phagocytic Capacity ◽  
Hematopoietic Stem ◽  
Gm Csf ◽  
Increased Risk ◽  
Macrophage Colony

Background. The myelodysplastic syndrome (MDS) comprises a group of clonal hematopoietic stem cell diseases characterized by cytopenia, dysplasia in one or more of the major myeloid lineages, ineffective hematopoiesis, and increased risk of development of acute myeloid leukemia (AML). Macrophages are innate immune cells that ingest and degrade abnormal cells, debris, and foreign material and orchestrate inflammatory processes. We analyzed the role of macrophages from MDS patients in vitro. Methods. Macrophages were induced from peripheral blood of patients with MDS via granulocyte macrophage colony-stimulating factor (GM-CSF). Phagocytic capacity of macrophages was measured with carboxyfluorescein succinimidyl ester and fluorescent microspheres. CD206 and signal regulatory protein alpha (SIRPα) on macrophages were detected by flow cytometry. Inducible nitric oxide synthase (iNOS) was measured by ELISA method. Results. Compared with normal control group, the number of monocytes increased in MDS patients. However, the monocytes showed impaired ability to induce macrophages and the number of macrophages induced from MDS samples was lower. Further, we demonstrated that the ex vivo phagocytic function of macrophages from MDS patients was impaired and levels of reorganization receptors CD206 and SIRPα were lower. Levels of iNOS secreted by macrophages in MDS were increased. Conclusions. Monocyte-derived macrophages are impaired in myelodysplastic syndromes.

scholarly journals FGFR2 gene polymorphism rs2981582 is associated with non-functioning pituitary adenomas in Chinese Han population: a case–control study

2018 ◽  
Vol 38 (6) ◽  
Author(s):  
Bin Zhu ◽  
Juan Wang ◽  
Lingling Qin ◽  
Lei Wang ◽  
Yanfei Zheng ◽  
...  
Keyword(s):  
Additive Model ◽  
Growth Factor Receptor ◽  
Recessive Model ◽  
Chinese Han ◽  
Fgfr2 Gene ◽  
Potential Association ◽  
Increased Risk ◽  
Significant Difference ◽  
Healthy Control

The association of the fibroblast growth factor receptor 2 gene (FGFR2) polymorphism rs2981582 with breast cancer has been extensively studied, whereas the role of this polymorphism in non-functioning pituitary adenoma (NFPA) has not been elucidated. We thus investigated a potential association of rs2981582 with NFPA. A total of 79 patients and 142 healthy control participants were enrolled in our study. DNA of the participants was extracted from peripheral blood samples and genotyped by using the MassARRAY method. We found that the AA genotype was associated with a higher risk of developing NFPA (OR = 1.743, 95%CI: 1.151–2.64, P=0.008). After adjusting for risk factors, significant difference was still observed between the two groups (OR = 1.862, 95%CI: 1.172–2.957, P=0.008). Moreover, under the assumptions of the recessive model (OR = 3.051, 95%CI: 1.403–6.635, P=0.005) and the additive model (AG: OR = 0.329, 95%CI: 0.144–0.755, P=0.009; AA: OR = 0.326, 95%CI: 0.141–0.757, P=0.009), rs2981582 was associated with an increased risk of NFPA. Our results proved that FGFR2 rs2981582 AA genotype was associated with a higher risk of NFPA. The recessive model and additive model also showed increased the risk of NFPA.

The role of MMP-2 and MMP-9 polymorphisms in sporadic intracranial aneurysms

2006 ◽  
Vol 105 (3) ◽  
pp. 418-423 ◽  
Author(s):  
Hariyadarshi Pannu ◽  
Dong H. Kim ◽  
Dongchuan Guo ◽  
Terri M. King ◽  
Grace Van Ginhoven ◽  
...  
Keyword(s):  
Vascular Remodeling ◽  
Intracranial Aneurysms ◽  
Caucasian Population ◽  
Gelatinase A ◽  
Ruptured Aneurysms ◽  
Increased Risk ◽  
Extracellular Matrix Components ◽  
Study Population ◽  
Matrix Components

Object Matrix metalloproteinases (MMPs) are a family of endopeptidases that mediate vascular remodeling by degrading extracellular matrix components, such as collagen and elastin. On the basis of accumulating evidence that implicates increased MMP-2 (gelatinase A) and MMP-9 (gelatinase B) amounts and activity in the pathogenesis of aneurysms, the authors investigated the genetic association between polymorphisms in MMP-2 and MMP-9 and sporadic intracranial aneurysms. Methods Eight polymorphisms located in MMP-2 and MMP-9 were genotyped, and the association of these variations with disease was assessed in a Caucasian population consisting of 125 patients with intracranial aneurysms and 234 ethnically matched healthy volunteers. Polymorphisms in the MMP-2 gene and the haplotypes generated from these polymorphisms were not associated with the occurrence of intracranial aneurysms. However, a polymorphism located in the 3′ untranslated region of MMP-9 showed a significant association with disease in the study population, with individuals carrying the TT genotype at increased risk for developing intracranial aneurysms (odds ratio 1.91, p = 0.005). Haplotypes containing the T allele of this polymorphism also showed a comparable association with disease. Similar results were obtained in an analysis of these polymorphisms in a subgroup of patients who presented with ruptured aneurysms. Conclusions The study findings support a role for MMP-9, but not MMP-2, in the pathogenesis of intracranial aneurysms.

scholarly journals Role of PTPRJ genotype in papillary thyroid carcinoma risk

2010 ◽  
Vol 17 (4) ◽  
pp. 1001-1006 ◽  
Author(s):  
Rodolfo Iuliano ◽  
Dario Palmieri ◽  
Huiling He ◽  
Angela Iervolino ◽  
Eleonora Borbone ◽  
...  
Keyword(s):  
Papillary Thyroid Carcinoma ◽  
Thyroid Carcinoma ◽  
Cancer Susceptibility ◽  
Tyrosine Phosphatase ◽  
Susceptibility Gene ◽  
Control Group ◽  
Papillary Thyroid ◽  
Genotype Frequencies ◽  
Increased Risk

The strong genetic predisposition to papillary thyroid carcinoma (PTC) might be due to a combination of low-penetrance susceptibility variants. Thus, the research into gene variants involved in the increase of susceptibility to PTC is a relevant field of investigation. The gene coding for the receptor-type tyrosine phosphatase PTPRJ has been proposed as a cancer susceptibility gene, and its role as a tumor suppressor gene is well established in thyroid carcinogenesis. In this study, we want to ascertain the role of PTPRJ genotype in the risk for PTC. We performed a case–control study in which we determined the PTPRJ genotype for the non-synonymous Gln276Pro and Asp872Glu polymorphisms by PCR amplification and sequencing. We calculated allele and genotype frequencies for the considered polymorphisms of PTPRJ in a total sample of 299 cases (PTC patients) and 339 controls (healthy subjects) selected from Caucasian populations. We observed a significantly higher frequency of homozygotes for the Asp872 allele in the group of PTC patients than in the control group (odds ratio=1.61, 95% confidence interval 1.15–2.25, P=0.0053). We observed a non-significant increased frequency of homozygotes for Gln276Pro polymorphism in PTC cases in two distinct Caucasian populations. Therefore, the results reported here show that the homozygous genotype for Asp872 of PTPRJ is associated with an increased risk to develop PTC.

Association of interleukin-1 gene polymorphisms with gastric cancer: A meta-analysis

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 21142-21142
Author(s):  
B. Vincenzi ◽  
D. Santini ◽  
G. Patti ◽  
F. Pantano ◽  
O. Venditti ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Meta Analysis ◽  
Interleukin 1 ◽  
Strong Association ◽  
Pooled Analysis ◽  
Epidemiologic Studies ◽  
Caucasian Population ◽  
Increased Risk ◽  
Stomach Adenocarcinoma

21142 Introduction: Previous studies on the association between interleukin-1 (IL-1) genetic polymorphisms and the risk of gastric cancer have produced conflicting results. The purpose of this study was to examine the association between IL-1 genotype and gastric cancer by systematically reviewing the original studies. Materials and Methods: We searched the MEDLINE, CENTRAL, and PubMed databases (last research performed on July 2005) and reviewed cited references to identify relevant studies. Search key words were: gastric cancer (OR stomach cancer OR gastric adenocarcinoma OR stomach adenocarcinoma) and IL-1 (OR IL1). The literature review identified 23 titles that met the search criteria. Data from 15 articles that investigated the association between any of IL-1B-511 and IL-1B-31 polymorphisms and gastric cancer met the inclusion criteria, and they were included in the meta-analysis. Eight studies evaluated the role of IL-1B-511, four the role of IL- 1B-31 and three investigated both IL-1B-511 and IL-1B-31. Results: By pooling all the studies identified, our study shows that individuals IL-1B-31T carrier have got an increased risk developing gastric cancer (OR of 1.25; 95% CI 1.06–1.47) in particular in Caucasian sub-group (OR of 1.41; 95% CI 0.97–2.05). IL-1B-31CC genotype confers a decreased risk (OR of 0.80; 95% CI 0.68–0.95) especially in Caucasian population (OR of 0.71; 95% CI 0.49–1.03) compared to Asians (OR of 0.83; 95% CI 0.69–0.99). This association might be explained with the well-known near complete linkage disequilibrium between IL1B-511T and IL1B-31C polymorphism. Furthermore our results suggest a strong association between IL1B-511T polymorphism and gastric cancer risk only in Caucasians and not in Asians. Conclusions: In conclusion, although affected by the common bias of each epidemiologic studies, this pooled analysis suggests that IL1B-511T polymorphism is associated with an increased risk of developing gastric cancer in Caucasian population. No significant financial relationships to disclose.

Sign in / Sign up

Export Citation Format

Share Document