Variants in TNF and NOS3 (eNOS) genes associated with sepsis in adult patients

Background Sepsis is a life‐threatening condition caused by a dysregulated host response to infections and is a leading cause of death in hospitalized patients. The present study aimed to elucidate the possible association between sepsis and the tumor necrosis factor (TNF) gene –308G/A (rs1800629) p...

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Veröffentlicht in:The journal of gene medicine 2021-04, Vol.23 (4), p.e3323-n/a
Hauptverfasser: Özkan, Mustafa, Günay, Nurullah, Sener, Elif Funda, Karcıoglu, Özgür, Tahtasakal, Reyhan, Dal, Fatma, Günay, Nahide Ekici, Demiryürek, Abdullah Tuncay
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container_title The journal of gene medicine
container_volume 23
creator Özkan, Mustafa
Günay, Nurullah
Sener, Elif Funda
Karcıoglu, Özgür
Tahtasakal, Reyhan
Dal, Fatma
Günay, Nahide Ekici
Demiryürek, Abdullah Tuncay
description Background Sepsis is a life‐threatening condition caused by a dysregulated host response to infections and is a leading cause of death in hospitalized patients. The present study aimed to elucidate the possible association between sepsis and the tumor necrosis factor (TNF) gene –308G/A (rs1800629) polymorphism, as well as endothelial nitric oxide synthase (eNOS, NOS3) gene –786T/C (rs2070744), 4a/4b (27 bp‐VNTR in intron 4, rs61722009) and 894G/T (Glu298Asp, rs1799983) polymorphisms. Methods In total, 188 septic adult cases and 188 healthy controls were enrolled. Genomic DNAs from the controls and patients were analyzed by polymerase chain reaction and restriction fragment length polymorphism methods. Results There were significant associations between the G/G genotype and G allele of the TNF –308G/A (rs1800629) polymorphism in the sepsis group (p 
doi_str_mv 10.1002/jgm.3323
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The present study aimed to elucidate the possible association between sepsis and the tumor necrosis factor (TNF) gene –308G/A (rs1800629) polymorphism, as well as endothelial nitric oxide synthase (eNOS, NOS3) gene –786T/C (rs2070744), 4a/4b (27 bp‐VNTR in intron 4, rs61722009) and 894G/T (Glu298Asp, rs1799983) polymorphisms. Methods In total, 188 septic adult cases and 188 healthy controls were enrolled. Genomic DNAs from the controls and patients were analyzed by polymerase chain reaction and restriction fragment length polymorphism methods. Results There were significant associations between the G/G genotype and G allele of the TNF –308G/A (rs1800629) polymorphism in the sepsis group (p &lt; 0.001). The presence of the T/C genotype (p = 0.002) and C allele (p = 0.001) of the –786T/C (rs2070744) was markedly associated with an increased risk of sepsis. However, no significant associations were found with 4a/4b (27 bp‐VNTR in intron 4, rs61722009) and 894G/T (Glu298Asp, rs1799983) polymorphisms. Higher 4bGC and lower 4bTT haplotype frequencies were associated with sepsis. Conclusions Our results strongly suggest that TNF gene (−308G/A, rs1800629) and NOS3 gene –786T/C (rs2070744) polymorphisms may modify individual susceptibility to sepsis in the Turkish population. The presence of the G/G genotype and G allele of the TNF‐α –308G/A (rs1800629) polymorphism, as well as the T/C genotype and C allele of the NOS3 –786T/C (rs2070744) polymorphism, were markedly associated with an increased risk of sepsis. Our study provides the first evidence that there are marked associations between 4bGC and 4bTT haplotypes and sepsis. The results of the present study show that these polymorphisms may modify individual susceptibility to sepsis in the Turkish population.</description><identifier>ISSN: 1099-498X</identifier><identifier>EISSN: 1521-2254</identifier><identifier>DOI: 10.1002/jgm.3323</identifier><identifier>PMID: 33609421</identifier><language>eng</language><publisher>England: Wiley Periodicals Inc</publisher><subject>Adolescent ; Adult ; Aged ; Aged, 80 and over ; Alleles ; endothelial nitric oxide synthase ; Female ; Gene Frequency ; Gene polymorphism ; Gene therapy ; Genetic Association Studies ; Genetic Predisposition to Disease ; Genotype ; Haplotypes ; Haplotypes - genetics ; Humans ; Male ; Middle Aged ; Nitric oxide ; Nitric Oxide Synthase Type III - genetics ; Nitric-oxide synthase ; NOS3 protein ; Polymerase chain reaction ; Polymorphism ; Polymorphism, Single Nucleotide - genetics ; Restriction fragment length polymorphism ; Risk Factors ; Sepsis ; Sepsis - blood ; Sepsis - genetics ; Sepsis - pathology ; susceptibility ; Tumor necrosis factor ; Tumor Necrosis Factor-alpha - genetics ; Tumor necrosis factor-TNF ; Young Adult</subject><ispartof>The journal of gene medicine, 2021-04, Vol.23 (4), p.e3323-n/a</ispartof><rights>2021 John Wiley &amp; Sons, Ltd.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3493-ef8b9bef127454caa826475635205072adb22404ccf516f10a7db58d9bb35edd3</citedby><cites>FETCH-LOGICAL-c3493-ef8b9bef127454caa826475635205072adb22404ccf516f10a7db58d9bb35edd3</cites><orcidid>0000-0003-1604-9565 ; 0000-0002-5644-5442</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Fjgm.3323$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fjgm.3323$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,776,780,1411,27901,27902,45550,45551</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/33609421$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Özkan, Mustafa</creatorcontrib><creatorcontrib>Günay, Nurullah</creatorcontrib><creatorcontrib>Sener, Elif Funda</creatorcontrib><creatorcontrib>Karcıoglu, Özgür</creatorcontrib><creatorcontrib>Tahtasakal, Reyhan</creatorcontrib><creatorcontrib>Dal, Fatma</creatorcontrib><creatorcontrib>Günay, Nahide Ekici</creatorcontrib><creatorcontrib>Demiryürek, Abdullah Tuncay</creatorcontrib><title>Variants in TNF and NOS3 (eNOS) genes associated with sepsis in adult patients</title><title>The journal of gene medicine</title><addtitle>J Gene Med</addtitle><description>Background Sepsis is a life‐threatening condition caused by a dysregulated host response to infections and is a leading cause of death in hospitalized patients. The present study aimed to elucidate the possible association between sepsis and the tumor necrosis factor (TNF) gene –308G/A (rs1800629) polymorphism, as well as endothelial nitric oxide synthase (eNOS, NOS3) gene –786T/C (rs2070744), 4a/4b (27 bp‐VNTR in intron 4, rs61722009) and 894G/T (Glu298Asp, rs1799983) polymorphisms. Methods In total, 188 septic adult cases and 188 healthy controls were enrolled. Genomic DNAs from the controls and patients were analyzed by polymerase chain reaction and restriction fragment length polymorphism methods. Results There were significant associations between the G/G genotype and G allele of the TNF –308G/A (rs1800629) polymorphism in the sepsis group (p &lt; 0.001). The presence of the T/C genotype (p = 0.002) and C allele (p = 0.001) of the –786T/C (rs2070744) was markedly associated with an increased risk of sepsis. However, no significant associations were found with 4a/4b (27 bp‐VNTR in intron 4, rs61722009) and 894G/T (Glu298Asp, rs1799983) polymorphisms. Higher 4bGC and lower 4bTT haplotype frequencies were associated with sepsis. Conclusions Our results strongly suggest that TNF gene (−308G/A, rs1800629) and NOS3 gene –786T/C (rs2070744) polymorphisms may modify individual susceptibility to sepsis in the Turkish population. The presence of the G/G genotype and G allele of the TNF‐α –308G/A (rs1800629) polymorphism, as well as the T/C genotype and C allele of the NOS3 –786T/C (rs2070744) polymorphism, were markedly associated with an increased risk of sepsis. Our study provides the first evidence that there are marked associations between 4bGC and 4bTT haplotypes and sepsis. The results of the present study show that these polymorphisms may modify individual susceptibility to sepsis in the Turkish population.</description><subject>Adolescent</subject><subject>Adult</subject><subject>Aged</subject><subject>Aged, 80 and over</subject><subject>Alleles</subject><subject>endothelial nitric oxide synthase</subject><subject>Female</subject><subject>Gene Frequency</subject><subject>Gene polymorphism</subject><subject>Gene therapy</subject><subject>Genetic Association Studies</subject><subject>Genetic Predisposition to Disease</subject><subject>Genotype</subject><subject>Haplotypes</subject><subject>Haplotypes - genetics</subject><subject>Humans</subject><subject>Male</subject><subject>Middle Aged</subject><subject>Nitric oxide</subject><subject>Nitric Oxide Synthase Type III - genetics</subject><subject>Nitric-oxide synthase</subject><subject>NOS3 protein</subject><subject>Polymerase chain reaction</subject><subject>Polymorphism</subject><subject>Polymorphism, Single Nucleotide - genetics</subject><subject>Restriction fragment length polymorphism</subject><subject>Risk Factors</subject><subject>Sepsis</subject><subject>Sepsis - blood</subject><subject>Sepsis - genetics</subject><subject>Sepsis - pathology</subject><subject>susceptibility</subject><subject>Tumor necrosis factor</subject><subject>Tumor Necrosis Factor-alpha - genetics</subject><subject>Tumor necrosis factor-TNF</subject><subject>Young Adult</subject><issn>1099-498X</issn><issn>1521-2254</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kMtKAzEUhoMotlbBJ5CAm7qYmuvMZCnFVqW2C6u4C5lJpqbMpU5mKH1704sKgqv_LL7zcc4PwCVGA4wQuV0uigGlhB6BLuYEB4RwduxnJETARPzeAWfOLRHCURyLU9ChNESCEdwF0zdVW1U2DtoSzqcjqEoNp7MXCvvGxw1cmNI4qJyrUqsao-HaNh_QmZWzux2l27yBK9VY4y3n4CRTuTMXh-yB19H9fPgQTGbjx-HdJEgpEzQwWZyIxGSYRIyzVKmYhCziIeUEcRQRpRNCGGJpmnEcZhipSCc81iJJKDda0x7o772ruvpsjWtkYV1q8lyVpmqdJExg_6AIuUev_6DLqq1Lf50kHAlCUMTCX2FaV87VJpOr2haq3kiM5LZj6TuW2449enUQtklh9A_4XaoHgj2wtrnZ_CuST-PnnfALAviCXA</recordid><startdate>202104</startdate><enddate>202104</enddate><creator>Özkan, Mustafa</creator><creator>Günay, Nurullah</creator><creator>Sener, Elif Funda</creator><creator>Karcıoglu, Özgür</creator><creator>Tahtasakal, Reyhan</creator><creator>Dal, Fatma</creator><creator>Günay, Nahide Ekici</creator><creator>Demiryürek, Abdullah Tuncay</creator><general>Wiley Periodicals Inc</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QP</scope><scope>7TK</scope><scope>7TM</scope><scope>8FD</scope><scope>FR3</scope><scope>K9.</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0003-1604-9565</orcidid><orcidid>https://orcid.org/0000-0002-5644-5442</orcidid></search><sort><creationdate>202104</creationdate><title>Variants in TNF and NOS3 (eNOS) genes associated with sepsis in adult patients</title><author>Özkan, Mustafa ; Günay, Nurullah ; Sener, Elif Funda ; Karcıoglu, Özgür ; Tahtasakal, Reyhan ; Dal, Fatma ; Günay, Nahide Ekici ; Demiryürek, Abdullah Tuncay</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3493-ef8b9bef127454caa826475635205072adb22404ccf516f10a7db58d9bb35edd3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>Adolescent</topic><topic>Adult</topic><topic>Aged</topic><topic>Aged, 80 and over</topic><topic>Alleles</topic><topic>endothelial nitric oxide synthase</topic><topic>Female</topic><topic>Gene Frequency</topic><topic>Gene polymorphism</topic><topic>Gene therapy</topic><topic>Genetic Association Studies</topic><topic>Genetic Predisposition to Disease</topic><topic>Genotype</topic><topic>Haplotypes</topic><topic>Haplotypes - genetics</topic><topic>Humans</topic><topic>Male</topic><topic>Middle Aged</topic><topic>Nitric oxide</topic><topic>Nitric Oxide Synthase Type III - genetics</topic><topic>Nitric-oxide synthase</topic><topic>NOS3 protein</topic><topic>Polymerase chain reaction</topic><topic>Polymorphism</topic><topic>Polymorphism, Single Nucleotide - genetics</topic><topic>Restriction fragment length polymorphism</topic><topic>Risk Factors</topic><topic>Sepsis</topic><topic>Sepsis - blood</topic><topic>Sepsis - genetics</topic><topic>Sepsis - pathology</topic><topic>susceptibility</topic><topic>Tumor necrosis factor</topic><topic>Tumor Necrosis Factor-alpha - genetics</topic><topic>Tumor necrosis factor-TNF</topic><topic>Young Adult</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Özkan, Mustafa</creatorcontrib><creatorcontrib>Günay, Nurullah</creatorcontrib><creatorcontrib>Sener, Elif Funda</creatorcontrib><creatorcontrib>Karcıoglu, Özgür</creatorcontrib><creatorcontrib>Tahtasakal, Reyhan</creatorcontrib><creatorcontrib>Dal, Fatma</creatorcontrib><creatorcontrib>Günay, Nahide Ekici</creatorcontrib><creatorcontrib>Demiryürek, Abdullah Tuncay</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Calcium &amp; 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The present study aimed to elucidate the possible association between sepsis and the tumor necrosis factor (TNF) gene –308G/A (rs1800629) polymorphism, as well as endothelial nitric oxide synthase (eNOS, NOS3) gene –786T/C (rs2070744), 4a/4b (27 bp‐VNTR in intron 4, rs61722009) and 894G/T (Glu298Asp, rs1799983) polymorphisms. Methods In total, 188 septic adult cases and 188 healthy controls were enrolled. Genomic DNAs from the controls and patients were analyzed by polymerase chain reaction and restriction fragment length polymorphism methods. Results There were significant associations between the G/G genotype and G allele of the TNF –308G/A (rs1800629) polymorphism in the sepsis group (p &lt; 0.001). The presence of the T/C genotype (p = 0.002) and C allele (p = 0.001) of the –786T/C (rs2070744) was markedly associated with an increased risk of sepsis. However, no significant associations were found with 4a/4b (27 bp‐VNTR in intron 4, rs61722009) and 894G/T (Glu298Asp, rs1799983) polymorphisms. Higher 4bGC and lower 4bTT haplotype frequencies were associated with sepsis. Conclusions Our results strongly suggest that TNF gene (−308G/A, rs1800629) and NOS3 gene –786T/C (rs2070744) polymorphisms may modify individual susceptibility to sepsis in the Turkish population. The presence of the G/G genotype and G allele of the TNF‐α –308G/A (rs1800629) polymorphism, as well as the T/C genotype and C allele of the NOS3 –786T/C (rs2070744) polymorphism, were markedly associated with an increased risk of sepsis. Our study provides the first evidence that there are marked associations between 4bGC and 4bTT haplotypes and sepsis. The results of the present study show that these polymorphisms may modify individual susceptibility to sepsis in the Turkish population.</abstract><cop>England</cop><pub>Wiley Periodicals Inc</pub><pmid>33609421</pmid><doi>10.1002/jgm.3323</doi><tpages>9</tpages><orcidid>https://orcid.org/0000-0003-1604-9565</orcidid><orcidid>https://orcid.org/0000-0002-5644-5442</orcidid></addata></record>
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subjects Adolescent
Adult
Aged
Aged, 80 and over
Alleles
endothelial nitric oxide synthase
Female
Gene Frequency
Gene polymorphism
Gene therapy
Genetic Association Studies
Genetic Predisposition to Disease
Genotype
Haplotypes
Haplotypes - genetics
Humans
Male
Middle Aged
Nitric oxide
Nitric Oxide Synthase Type III - genetics
Nitric-oxide synthase
NOS3 protein
Polymerase chain reaction
Polymorphism
Polymorphism, Single Nucleotide - genetics
Restriction fragment length polymorphism
Risk Factors
Sepsis
Sepsis - blood
Sepsis - genetics
Sepsis - pathology
susceptibility
Tumor necrosis factor
Tumor Necrosis Factor-alpha - genetics
Tumor necrosis factor-TNF
Young Adult
title Variants in TNF and NOS3 (eNOS) genes associated with sepsis in adult patients
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