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Open accessJournal ArticleDOI: 10.1038/S41598-021-84645-4

Polymorphisms of the matrix metalloproteinase genes are associated with essential hypertension in a Caucasian population of Central Russia

04 Mar 2021-Scientific Reports (Springer Science and Business Media LLC)-Vol. 11, Iss: 1, pp 5224-5224
Abstract: This study aimed to determine possible association of eight polymorphisms of seven MMP genes with essential hypertension (EH) in a Caucasian population of Central Russia. Eight SNPs of the MMP1, MMP2, MMP3, MMP7, MMP8, MMP9, and MMP12 genes and their gene-gene (epistatic) interactions were analyzed for association with EH in a cohort of 939 patients and 466 controls using logistic regression and assuming additive, recessive, and dominant genetic models. The functional significance of the polymorphisms associated with EH and 114 variants linked to them (r2 ≥ 0.8) was analyzed in silico. Allele G of rs11568818 MMP7 was associated with EH according to all three genetic models (OR = 0.58-0.70, pperm = 0.01-0.03). The above eight SNPs were associated with the disorder within 12 most significant epistatic models (OR = 1.49-1.93, pperm < 0.02). Loci rs1320632 MMP8 and rs11568818 MMP7 contributed to the largest number of the models (12 and 10, respectively). The EH-associated loci and 114 SNPs linked to them had non-synonymous, regulatory, and eQTL significance for 15 genes, which contributed to the pathways related to metalloendopeptidase activity, collagen degradation, and extracellular matrix disassembly. In summary, eight studied SNPs of MMPs genes were associated with EH in the Caucasian population of Central Russia.

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5 results found

Journal ArticleDOI: 10.1080/13816810.2021.1955275
Abstract: PURPOSE To replicate the finding of the association of five CDKN2B-AS1 gene polymorphisms (rs7865618, rs1063192, rs944800, rs2157719, and rs4977756) with primary open-angle glaucoma (POAG) and to analyze them for possible association with pseudoexfoliation glaucoma (PXFG) in a Caucasian population of Central Russia. METHODS A total of 932 participants of Russian ethnicity (self-reported), including 328 patients with PXFG, 208 patients with POAG (high-tension glaucoma), and 396 controls, were enrolled in the study. The SNPs were analyzed for possible associations using logistic regression. RESULTS Several haplotypes based on the studied SNPs were associated with POAG (three haplotypes) and PXFG (six haplotypes). Haplotype AAAGG of loci rs1063192-rs7865618-rs2157719-rs944800-rs4977756 conferred the highest risk for both POAG (OR = 3.99, рperm = 0.001) and PXFG (OR = 2.84, рperm = 0.001). CONCLUSIONS The CDKN2B-AS1 gene was associated with an increased risk of both POAG and PXFG in Caucasians of Central Russia. The gene may be related to the development of various types of glaucoma.

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Topics: Glaucoma (53%), Open angle glaucoma (52%)

3 Citations

Open accessJournal ArticleDOI: 10.1038/S41598-021-92527-Y
29 Jun 2021-Scientific Reports
Abstract: This study analyzed the association of functionally significant SNPs of matrix metalloproteinase (MMP) genes in the development of peptic ulcer disease (PUD) in Caucasians from Central Russia. Ten SNPs of the MMP-1, MMP-2, MMP-3, MMP-8, and MMP-9 genes were analyzed for association with PUD in a cohort of 798 patients with PUD (including 404 H. pylori-positive and 394 H. pylori-negative) and 347 H. pylori-negative controls using logistic regression and assuming the additive, recessive, and dominant genetic models. The variants of MMP-1, MMP-2, MMP-3, and MMP-8 did not manifest any significant associations with the diseases. Five SNPs of the MMP-9 gene demonstrated such association. Allele G of the rs17576 MMP-9 locus conferred a higher risk for PUD (ORadj = 1.31, pperm = 0.016), haplotype AACG of loci rs17576-rs3787268-rs2250889-rs17577 of the MMP-9 gene decreased risk for PUD (ORadj = 0.17, pperm = 0.003). Also, allele C of rs3918249, allele G of rs17576 and haplotype CG of rs3918249-rs17576 of the MMP-9 gene increased risk for H. pylori-positive PUD (ORadj = 1.82, pperm = 0.002; ORadj = 1.53-1.95 pperm = 0.001-0.013 and ORadj = 1.49 pperm = 0.009 respectively). The above loci and 50 linked to them possess significant regulatory effects and may affect the alternative splicing of four genes and the expression of 17 genes in various organs and tissues related to the PUD pathogenesis.

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Topics: Single-nucleotide polymorphism (53%), Allele (52%), Haplotype (51%) ... show more

1 Citations

Open accessJournal ArticleDOI: 10.1371/JOURNAL.PONE.0257060
07 Sep 2021-PLOS ONE
Abstract: Background and purpose The study analyzed the association of functionally significant polymorphisms of matrix metalloproteinases (MMPs) genes with the development of gastric ulcer (GU) in Caucasians from Central Russia. Methods The 781 participants, including 434 patients with GU (196 Helicobacter pylori (H. pylori)-positive and 238 H. pylori-negative) and 347 controls (all H. pylori-negative) were recruited for the study. Ten SNPs of the MMP1 (rs1799750), MMP2 (rs243865), MMP3 (rs679620), MMP8 (rs1940475), and MMP9 (rs3918242, rs3918249, rs3787268, rs17576, rs17577, and rs2250889) genes were considered for association with GU using multiple logistic regression. The SNPs associated with GU and loci linked (r2≥0.8) to them were analyzed in silico for their functional assignments. Results The SNPs of the MMP9 gene were associated with H. pylori-positive GU: alleles C of rs3918249 (OR = 2.02, pperm = 0.008) and A of rs3787268 (OR = 1.60–1.82, pperm ≤ 0.016), and eight haplotypes of all studied MMP9 gene SNPs (OR = 1.85–2.04, pperm ≤ 0.016) increased risk for H. pylori-positive GU. None of the analyzed SNPs was independently associated with GU and H. pylori-negative GU. Two haplotypes of the MMP9 gene (contributed by rs3918242, rs3918249, rs17576, and rs3787268) increased risk for GU (OR = 1.62–1.65, pperm ≤ 0.006). Six loci of the MMP9 gene, which are associated with H. pylori-positive GU, and 65 SNPs linked to them manifest significant epigenetic effects, have pronounced eQTL (17 genes) and sQTL (6 genes) values. Conclusion SNPs of the MMP9 were associated with H. pylori-positive GU but not with H. pylori-negative GU in Caucasians of Central Russia.

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Journal ArticleDOI: 10.1134/S1022795421100082
Abstract: Gender-specific features of associations of functionally significant polymorphic loci of matrix metalloproteinase genes with the development of peptic ulcer disease (PUD) in the population of the European part of Russia were studied. The study included 305 men (patients with PUD—188, control group—117) and 441 women (patients with PUD—211, control group—230). Ten functionally significant polymorphic loci of matrix metalloproteinase genes were genotyped: rs1799750 MMP1, rs243865 MMP2, rs679620 MMP3, rs1940475 MMP8, rs3918242, rs3918249, rs17576, rs3787268, rs2250889, rs17577 of the MMP9 gene. Associations of polymorphic loci of MMP genes with PUD were studied by logistic regression (dominant, recessive, and additive genetic models of allele interaction were evaluated). It was found that alleles C rs3918249 (OR = 1.61, pperm = 0.048) and G rs17576 (OR = 1.48–2.08, pperm ≤ 0.042) of the MMP9 gene were risk factors for the occurrence of PUD in men. In women, the 2G rs1799750 allele of the MMP1 gene had a protective value for the development of the disease (OR = 0.74, pperm = 0.047). Polymorphic loci associated with PUD in men and women exhibit pronounced epigenetic effects (they affect the affinity of DNA motifs for various transcription factors, are located in the region of promoters and enhancers in the stomach and duodenum, and are associated with gene expression in various parts of the digestive system). Gender-specific features of associations of polymorphism of MMP genes with the development of PUD were revealed: rs3918249 and rs17576 of the MMP9 gene determine the susceptibility to the development of PUD in men, and rs1799750 of the MMP1 gene determines the susceptibility in women.

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Topics: Allele (52%), Genetic model (52%), Population (52%)

Journal ArticleDOI: 10.1134/S1022795421090039
Abstract: We studied the associations of newborn weight with polymorphic loci of growth factor genes in pregnant women with preeclampsia (PE) and considered their regulatory potential. In the group of pregnant women with PE (n = 190), a molecular genetic study of five polymorphic loci of growth factor genes was performed: rs4444903 EGF, rs833061 VEGFA, rs2981582 FGFR2, rs6214 IGF1, rs1800469 TGFβ1. Newborn somatometry was performed using standard methods. Associations of the studied polymorphic loci with newborn weight were studied using log-linear regression analysis. It was found that the genetic risk factor for the birth of small children in pregnant women with PE is the allele C of the rs833061 polymorphism of the VEGFA gene (pperm = 0.002): women with the T/T genotype have the highest newborn weight (on average 3524 g), while women with the C/C genotype have the minimum newborn weight (on average 3415 g). It is shown that the allele C of polymorphic locus rs833061 is associated with low transcription of the VEGFA gene in the thyroid gland and a higher level of alternative splicing of the VEGFA gene transcript in skeletal muscle, increases the affinity of DNA for transcription factors BCL, Pax-5, and Znf143, and affects the interaction of DNA with more than 20 different regulatory proteins (CTCF, RAD21, ZNF263, MAX, etc.). It is revealed that polymorphism rs833061of the VEGF gene in pregnant women with PE is associated with weight of the newborn and has considerable regulatory potential.

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Topics: Locus (genetics) (52%), Genotype (52%), Allele (51%)

60 results found

Open accessJournal ArticleDOI: 10.1093/EURHEARTJ/EHS092
Massimo Piepoli1, Arno W. Hoes, Stefan Agewall2, Christian Albus  +22 moreInstitutions (5)
Abstract: ABI : ankle–brachial index ACCORD : Action to Control Cardiovascular Risk in Diabetes ADVANCE : Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation AGREE : Appraisal of Guidelines Research and Evaluation AHA : American Heart Association apoA1 : apolipoprotein A1 apoB : apolipoprotein B CABG : coronary artery bypass graft surgery CARDS : Collaborative AtoRvastatin Diabetes Study CCNAP : Council on Cardiovascular Nursing and Allied Professions CHARISMA : Clopidogrel for High Athero-thrombotic Risk and Ischemic Stabilisation, Management, and Avoidance CHD : coronary heart disease CKD : chronic kidney disease COMMIT : Clopidogrel and Metoprolol in Myocardial Infarction Trial CRP : C-reactive protein CURE : Clopidogrel in Unstable Angina to Prevent Recurrent Events CVD : cardiovascular disease DALYs : disability-adjusted life years DBP : diastolic blood pressure DCCT : Diabetes Control and Complications Trial ED : erectile dysfunction eGFR : estimated glomerular filtration rate EHN : European Heart Network EPIC : European Prospective Investigation into Cancer and Nutrition EUROASPIRE : European Action on Secondary and Primary Prevention through Intervention to Reduce Events GFR : glomerular filtration rate GOSPEL : Global Secondary Prevention Strategies to Limit Event Recurrence After MI GRADE : Grading of Recommendations Assessment, Development and Evaluation HbA1c : glycated haemoglobin HDL : high-density lipoprotein HF-ACTION : Heart Failure and A Controlled Trial Investigating Outcomes of Exercise TraiNing HOT : Hypertension Optimal Treatment Study HPS : Heart Protection Study HR : hazard ratio hsCRP : high-sensitivity C-reactive protein HYVET : Hypertension in the Very Elderly Trial ICD : International Classification of Diseases IMT : intima-media thickness INVEST : International Verapamil SR/Trandolapril JTF : Joint Task Force LDL : low-density lipoprotein Lp(a) : lipoprotein(a) LpPLA2 : lipoprotein-associated phospholipase 2 LVH : left ventricular hypertrophy MATCH : Management of Atherothrombosis with Clopidogrel in High-risk Patients with Recent Transient Ischaemic Attack or Ischaemic Stroke MDRD : Modification of Diet in Renal Disease MET : metabolic equivalent MONICA : Multinational MONItoring of trends and determinants in CArdiovascular disease NICE : National Institute of Health and Clinical Excellence NRT : nicotine replacement therapy NSTEMI : non-ST elevation myocardial infarction ONTARGET : Ongoing Telmisartan Alone and in combination with Ramipril Global Endpoint Trial OSA : obstructive sleep apnoea PAD : peripheral artery disease PCI : percutaneous coronary intervention PROactive : Prospective Pioglitazone Clinical Trial in Macrovascular Events PWV : pulse wave velocity QOF : Quality and Outcomes Framework RCT : randomized clinical trial RR : relative risk SBP : systolic blood pressure SCORE : Systematic Coronary Risk Evaluation Project SEARCH : Study of the Effectiveness of Additional Reductions in Cholesterol and SHEP : Systolic Hypertension in the Elderly Program STEMI : ST-elevation myocardial infarction SU.FOL.OM3 : SUpplementation with FOlate, vitamin B6 and B12 and/or OMega-3 fatty acids Syst-Eur : Systolic Hypertension in Europe TNT : Treating to New Targets UKPDS : United Kingdom Prospective Diabetes Study VADT : Veterans Affairs Diabetes Trial VALUE : Valsartan Antihypertensive Long-term Use VITATOPS : VITAmins TO Prevent Stroke VLDL : very low-density lipoprotein WHO : World Health Organization ### 1.1 Introduction Atherosclerotic cardiovascular disease (CVD) is a chronic disorder developing insidiously throughout life and usually progressing to an advanced stage by the time symptoms occur. It remains the major cause of premature death in Europe, even though CVD mortality has …

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6,913 Citations

Journal ArticleDOI: 10.1038/NPROT.2009.86
Priyank Kumar1, Steven Henikoff2, Steven Henikoff3, Pauline C. Ng1  +1 moreInstitutions (3)
25 Jun 2009-Nature Protocols
Abstract: The effect of genetic mutation on phenotype is of significant interest in genetics. The type of genetic mutation that causes a single amino acid substitution (AAS) in a protein sequence is called a non-synonymous single nucleotide polymorphism (nsSNP). An nsSNP could potentially affect the function of the protein, subsequently altering the carrier's phenotype. This protocol describes the use of the 'Sorting Tolerant From Intolerant' (SIFT) algorithm in predicting whether an AAS affects protein function. To assess the effect of a substitution, SIFT assumes that important positions in a protein sequence have been conserved throughout evolution and therefore substitutions at these positions may affect protein function. Thus, by using sequence homology, SIFT predicts the effects of all possible substitutions at each position in the protein sequence. The protocol typically takes 5–20 min, depending on the input. SIFT is available as an online tool ( ).

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Topics: Protein sequencing (51%)

5,634 Citations

Open accessJournal ArticleDOI: 10.1093/EURHEARTJ/EHM316
Joep Perk1, G. De Backer2, Helmut Gohlke2, Ian D. Graham  +23 moreInstitutions (5)
Abstract: Guidelines and Expert Consensus Documents summarize and evaluate all currently available evidence on a particular issue with the aim to assist physicians in selecting the best management strategies for a typical patient, suffering from a given condition, taking into account the impact on outcome, as well as the risk–benefit ratio of particular diagnostic or therapeutic means. Guidelines are not substitutes for textbooks. The legal implications of medical guidelines have been discussed previously. A great number of Guidelines and Expert Consensus Documents have been issued in recent years by the European Society of Cardiology (ESC) as well as by other societies and organizations. Because of the impact on clinical practice, quality criteria for development of guidelines have been established in order to make all decisions transparent to the user. The recommendations for formulating and issuing ESC Guidelines and Expert Consensus Documents can be found on the ESC web site ( In brief, experts in the field are selected and undertake a comprehensive review of the published evidence for management and/or prevention of a given condition. A critical evaluation of diagnostic and therapeutic procedures is performed, including assessment of the risk–benefit ratio. Estimates of expected health outcomes for larger societies are included, where data exist. The level of evidence and the strength of recommendation of particular treatment options are weighed and graded according to predefined scales, as outlined in the tables below. The experts of the writing panels have provided disclosure statements of all relationships they may have which might be perceived as real or potential sources of conflicts of interest. These disclosure forms are kept on file at the European Heart House, headquarters of the ESC. Any changes in conflict of interest that arise during the writing period must be notified to the ESC. The Task Force report was entirely …

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3,198 Citations

Open accessJournal ArticleDOI: 10.1038/NATURE24277
12 Oct 2017-Nature
Abstract: Characterization of the molecular function of the human genome and its variation across individuals is essential for identifying the cellular mechanisms that underlie human genetic traits and diseases. The Genotype-Tissue Expression (GTEx) project aims to characterize variation in gene expression levels across individuals and diverse tissues of the human body, many of which are not easily accessible. Here we describe genetic effects on gene expression levels across 44 human tissues. We find that local genetic variation affects gene expression levels for the majority of genes, and we further identify inter-chromosomal genetic effects for 93 genes and 112 loci. On the basis of the identified genetic effects, we characterize patterns of tissue specificity, compare local and distal effects, and evaluate the functional properties of the genetic effects. We also demonstrate that multi-tissue, multi-individual data can be used to identify genes and pathways affected by human disease-associated variation, enabling a mechanistic interpretation of gene regulation and the genetic basis of disease.

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2,449 Citations

Open accessJournal ArticleDOI: 10.1093/NAR/GKQ537
David Warde-Farley1, Sylva L. Donaldson1, Ovi Comes1, Khalid Zuberi1  +13 moreInstitutions (1)
Abstract: GeneMANIA ( is a flexible, user-friendly web interface for generating hypotheses about gene function, analyzing gene lists and prioritizing genes for functional assays. Given a query list, GeneMANIA extends the list with functionally similar genes that it identifies using available genomics and proteomics data. GeneMANIA also reports weights that indicate the predictive value of each selected data set for the query. Six organisms are currently supported (Arabidopsis thaliana, Caenorhabditis elegans, Drosophila melanogaster, Mus musculus, Homo sapiens and Saccharomyces cerevisiae) and hundreds of data sets have been collected from GEO, BioGRID, Pathway Commons and I2D, as well as organism-specific functional genomics data sets. Users can select arbitrary subsets of the data sets associated with an organism to perform their analyses and can upload their own data sets to analyze. The GeneMANIA algorithm performs as well or better than other gene function prediction methods on yeast and mouse benchmarks. The high accuracy of the GeneMANIA prediction algorithm, an intuitive user interface and large database make GeneMANIA a useful tool for any biologist.

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2,327 Citations

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