Functional polymorphisms in transforming growth factor-beta-1 (TGFβ-1) and vascular endothelial growth factor (VEGF) genes modify risk of renal parenchymal scarring following childhood urinary tract infection
Background. The risk of renal scar formation following urinary tract infection (UTI) varies markedly between individuals. We sought to investigate a possible role of the common polymorphisms in the gene encoding for VEGF and TGFβ-1, key regulators of tissue repair, in renal scarring. Methods. Acute...
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| description | Background. The risk of renal scar formation following urinary tract infection (UTI) varies markedly between individuals. We sought to investigate a possible role of the common polymorphisms in the gene encoding for VEGF and TGFβ-1, key regulators of tissue repair, in renal scarring. Methods. Acute pyelonephritis was diagnosed in 104 children (63 males) aged 2 months to 12 years by urine culture and 99Tc-DMSA renal scan. A follow-up isotope scan was performed 4–6 months later to identify new renal scar formation. Vesicoureteral reflux (VUR) was examined by micturating cystourethrogram. Controls comprised 300 healthy children with no evidence of renal disease. Three single-nucleotide polymorphisms (SNPs) in the TGFβ-1 (−800 A/G, −509 C/T and 869 C/T) and four SNPs in the VEGF gene (−2578 C/A, −1154 G/A, −460 T/C and +405 G/C) were genotyped in all subjects. Results. Forty-six of the 104 patients developed renal parenchymal scarring (44.2%). VUR was found in 35.6%. The −509 T allele in the TGFβ-1 promoter was significantly more common in cases with renal scarring (51%) than in non-scarring patients (22.4%) and controls (23.6%) (both P < 0.0001). At the haplotype level, the GTC combination at −800/−509/+869 was strongly associated with renal scarring (P = 0.0002). VEGF−460 CC was more common in UTI cases with renal scarring than in non-scarring patients and controls (P = 0.03 and 0.001, respectively). Multiple logistic regression testing identified the presence of VUR (odds ratio 12.4, CI 3.8–40; P < 0.001) and the TGFβ-1 −509 T allele (OR 6.1, CI 2.4–15.5; P < 0.001) as independent risk factors for renal scarring after UTI. In contrast, age, gender and the type of underlying organism were not predictive of renal scarring. Conclusions. Activating variants in the TGFβ-1 and VEGF gene promoters are associated with post-UTI renal scar formation in children. The TGFβ-1 509T allele predicts renal scarring independent of VUR. |
| doi_str_mv | 10.1093/ndt/gfp532 |
| format | Article |
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The risk of renal scar formation following urinary tract infection (UTI) varies markedly between individuals. We sought to investigate a possible role of the common polymorphisms in the gene encoding for VEGF and TGFβ-1, key regulators of tissue repair, in renal scarring. Methods. Acute pyelonephritis was diagnosed in 104 children (63 males) aged 2 months to 12 years by urine culture and 99Tc-DMSA renal scan. A follow-up isotope scan was performed 4–6 months later to identify new renal scar formation. Vesicoureteral reflux (VUR) was examined by micturating cystourethrogram. Controls comprised 300 healthy children with no evidence of renal disease. Three single-nucleotide polymorphisms (SNPs) in the TGFβ-1 (−800 A/G, −509 C/T and 869 C/T) and four SNPs in the VEGF gene (−2578 C/A, −1154 G/A, −460 T/C and +405 G/C) were genotyped in all subjects. Results. Forty-six of the 104 patients developed renal parenchymal scarring (44.2%). VUR was found in 35.6%. The −509 T allele in the TGFβ-1 promoter was significantly more common in cases with renal scarring (51%) than in non-scarring patients (22.4%) and controls (23.6%) (both P < 0.0001). At the haplotype level, the GTC combination at −800/−509/+869 was strongly associated with renal scarring (P = 0.0002). VEGF−460 CC was more common in UTI cases with renal scarring than in non-scarring patients and controls (P = 0.03 and 0.001, respectively). Multiple logistic regression testing identified the presence of VUR (odds ratio 12.4, CI 3.8–40; P < 0.001) and the TGFβ-1 −509 T allele (OR 6.1, CI 2.4–15.5; P < 0.001) as independent risk factors for renal scarring after UTI. In contrast, age, gender and the type of underlying organism were not predictive of renal scarring. Conclusions. Activating variants in the TGFβ-1 and VEGF gene promoters are associated with post-UTI renal scar formation in children. The TGFβ-1 509T allele predicts renal scarring independent of VUR.</description><identifier>ISSN: 0931-0509</identifier><identifier>EISSN: 1460-2385</identifier><identifier>DOI: 10.1093/ndt/gfp532</identifier><identifier>PMID: 19861314</identifier><identifier>CODEN: NDTREA</identifier><language>eng</language><publisher>Oxford: Oxford University Press</publisher><subject>Alleles ; Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy ; Biological and medical sciences ; Case-Control Studies ; Child ; Child, Preschool ; Cicatrix - genetics ; Emergency and intensive care: renal failure. Dialysis management ; Female ; Genetic Predisposition to Disease - genetics ; Genotype ; haplotypes ; Haplotypes - genetics ; Humans ; Infant ; Intensive care medicine ; Kidney ; Logistic Models ; Male ; Medical sciences ; Nephrology. Urinary tract diseases ; Nephropathies. Renovascular diseases. Renal failure ; Polymorphism, Single Nucleotide - genetics ; polymorphisms ; renal ; Renal failure ; scarring ; TGFB1 ; Transforming Growth Factor beta1 - genetics ; Urinary Tract Infections - complications ; Vascular Endothelial Growth Factor A - genetics</subject><ispartof>Nephrology, dialysis, transplantation, 2010-03, Vol.25 (3), p.779-785</ispartof><rights>Oxford University Press © The Author 2009. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved. For Permissions, please e-mail: journals.permissions@oxfordjournals.org 2009</rights><rights>2015 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c384t-768465521ec33ee42ddef24346ea7cad954c42ffd8fb55e82563f7642aab2d2f3</citedby><cites>FETCH-LOGICAL-c384t-768465521ec33ee42ddef24346ea7cad954c42ffd8fb55e82563f7642aab2d2f3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,1584,27924,27925</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=22680556$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/19861314$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Hussein, Almontaser</creatorcontrib><creatorcontrib>Askar, Eman</creatorcontrib><creatorcontrib>Elsaeid, Moustafa</creatorcontrib><creatorcontrib>Schaefer, Franz</creatorcontrib><title>Functional polymorphisms in transforming growth factor-beta-1 (TGFβ-1) and vascular endothelial growth factor (VEGF) genes modify risk of renal parenchymal scarring following childhood urinary tract infection</title><title>Nephrology, dialysis, transplantation</title><addtitle>Nephrol Dial Transplant</addtitle><addtitle>Nephrol Dial Transplant</addtitle><description>Background. The risk of renal scar formation following urinary tract infection (UTI) varies markedly between individuals. We sought to investigate a possible role of the common polymorphisms in the gene encoding for VEGF and TGFβ-1, key regulators of tissue repair, in renal scarring. Methods. Acute pyelonephritis was diagnosed in 104 children (63 males) aged 2 months to 12 years by urine culture and 99Tc-DMSA renal scan. A follow-up isotope scan was performed 4–6 months later to identify new renal scar formation. Vesicoureteral reflux (VUR) was examined by micturating cystourethrogram. Controls comprised 300 healthy children with no evidence of renal disease. Three single-nucleotide polymorphisms (SNPs) in the TGFβ-1 (−800 A/G, −509 C/T and 869 C/T) and four SNPs in the VEGF gene (−2578 C/A, −1154 G/A, −460 T/C and +405 G/C) were genotyped in all subjects. Results. Forty-six of the 104 patients developed renal parenchymal scarring (44.2%). VUR was found in 35.6%. The −509 T allele in the TGFβ-1 promoter was significantly more common in cases with renal scarring (51%) than in non-scarring patients (22.4%) and controls (23.6%) (both P < 0.0001). At the haplotype level, the GTC combination at −800/−509/+869 was strongly associated with renal scarring (P = 0.0002). VEGF−460 CC was more common in UTI cases with renal scarring than in non-scarring patients and controls (P = 0.03 and 0.001, respectively). Multiple logistic regression testing identified the presence of VUR (odds ratio 12.4, CI 3.8–40; P < 0.001) and the TGFβ-1 −509 T allele (OR 6.1, CI 2.4–15.5; P < 0.001) as independent risk factors for renal scarring after UTI. In contrast, age, gender and the type of underlying organism were not predictive of renal scarring. Conclusions. Activating variants in the TGFβ-1 and VEGF gene promoters are associated with post-UTI renal scar formation in children. The TGFβ-1 509T allele predicts renal scarring independent of VUR.</description><subject>Alleles</subject><subject>Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy</subject><subject>Biological and medical sciences</subject><subject>Case-Control Studies</subject><subject>Child</subject><subject>Child, Preschool</subject><subject>Cicatrix - genetics</subject><subject>Emergency and intensive care: renal failure. Dialysis management</subject><subject>Female</subject><subject>Genetic Predisposition to Disease - genetics</subject><subject>Genotype</subject><subject>haplotypes</subject><subject>Haplotypes - genetics</subject><subject>Humans</subject><subject>Infant</subject><subject>Intensive care medicine</subject><subject>Kidney</subject><subject>Logistic Models</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Nephrology. Urinary tract diseases</subject><subject>Nephropathies. Renovascular diseases. Renal failure</subject><subject>Polymorphism, Single Nucleotide - genetics</subject><subject>polymorphisms</subject><subject>renal</subject><subject>Renal failure</subject><subject>scarring</subject><subject>TGFB1</subject><subject>Transforming Growth Factor beta1 - genetics</subject><subject>Urinary Tract Infections - complications</subject><subject>Vascular Endothelial Growth Factor A - genetics</subject><issn>0931-0509</issn><issn>1460-2385</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2010</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kctuEzEUhi0EoiGw4QGQN4gWaej4NpclqpoUUcSmXNSN5fiSMfWMp7aHktfiQZB4I5wmCmLD6hzpfP7Pf_wD8ByVb1DZktNBpdO1GRnBD8AM0aosMGnYQzDLQ1SUrGyPwJMYv5Vl2eK6fgyOUNtUiCA6A78X0yCT9YNwcPRu0_swdjb2EdoBpiCGaHzo7bCG6-DvUgeNkMmHYqWTKBA8vloufv0s0AkUg4LfRZSTEwHqQfnUaWez6j_v4PHn8-XiBK71oCPsvbJmA4ONN9AbGPS9C5Gr7DZ97qMUIWyXG--cv9t2srNOdd4rOOWJCJutS5myXaPvD3kKHhnhon62r3PwaXF-dXZRXH5cvjt7e1lI0tBU1FVDK8Yw0pIQrSlWShtMCa20qKVQLaOSYmNUY1aM6Qazipi6oliIFVbYkDl4tdMdg7-ddEy8t1Fq58Sg_RR5TQgihOYM5uD1jpTBxxi04WOwfbbOUcm3CfKcIN8lmOEXe9lp1Wv1F91HloGXeyD_tnAmZyRtPHAYV03JstkD56fx_wuLHWdj0j8OpAg3vKpJzfjF12v-4UuFmwa_59fkDw-Oxlo</recordid><startdate>20100301</startdate><enddate>20100301</enddate><creator>Hussein, Almontaser</creator><creator>Askar, Eman</creator><creator>Elsaeid, Moustafa</creator><creator>Schaefer, Franz</creator><general>Oxford University Press</general><scope>BSCLL</scope><scope>IQODW</scope><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>7X8</scope></search><sort><creationdate>20100301</creationdate><title>Functional polymorphisms in transforming growth factor-beta-1 (TGFβ-1) and vascular endothelial growth factor (VEGF) genes modify risk of renal parenchymal scarring following childhood urinary tract infection</title><author>Hussein, Almontaser ; Askar, Eman ; Elsaeid, Moustafa ; Schaefer, Franz</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c384t-768465521ec33ee42ddef24346ea7cad954c42ffd8fb55e82563f7642aab2d2f3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2010</creationdate><topic>Alleles</topic><topic>Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy</topic><topic>Biological and medical sciences</topic><topic>Case-Control Studies</topic><topic>Child</topic><topic>Child, Preschool</topic><topic>Cicatrix - genetics</topic><topic>Emergency and intensive care: renal failure. Dialysis management</topic><topic>Female</topic><topic>Genetic Predisposition to Disease - genetics</topic><topic>Genotype</topic><topic>haplotypes</topic><topic>Haplotypes - genetics</topic><topic>Humans</topic><topic>Infant</topic><topic>Intensive care medicine</topic><topic>Kidney</topic><topic>Logistic Models</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Nephrology. Urinary tract diseases</topic><topic>Nephropathies. Renovascular diseases. Renal failure</topic><topic>Polymorphism, Single Nucleotide - genetics</topic><topic>polymorphisms</topic><topic>renal</topic><topic>Renal failure</topic><topic>scarring</topic><topic>TGFB1</topic><topic>Transforming Growth Factor beta1 - genetics</topic><topic>Urinary Tract Infections - complications</topic><topic>Vascular Endothelial Growth Factor A - genetics</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Hussein, Almontaser</creatorcontrib><creatorcontrib>Askar, Eman</creatorcontrib><creatorcontrib>Elsaeid, Moustafa</creatorcontrib><creatorcontrib>Schaefer, Franz</creatorcontrib><collection>Istex</collection><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Nephrology, dialysis, transplantation</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Hussein, Almontaser</au><au>Askar, Eman</au><au>Elsaeid, Moustafa</au><au>Schaefer, Franz</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Functional polymorphisms in transforming growth factor-beta-1 (TGFβ-1) and vascular endothelial growth factor (VEGF) genes modify risk of renal parenchymal scarring following childhood urinary tract infection</atitle><jtitle>Nephrology, dialysis, transplantation</jtitle><stitle>Nephrol Dial Transplant</stitle><addtitle>Nephrol Dial Transplant</addtitle><date>2010-03-01</date><risdate>2010</risdate><volume>25</volume><issue>3</issue><spage>779</spage><epage>785</epage><pages>779-785</pages><issn>0931-0509</issn><eissn>1460-2385</eissn><coden>NDTREA</coden><abstract>Background. The risk of renal scar formation following urinary tract infection (UTI) varies markedly between individuals. We sought to investigate a possible role of the common polymorphisms in the gene encoding for VEGF and TGFβ-1, key regulators of tissue repair, in renal scarring. Methods. Acute pyelonephritis was diagnosed in 104 children (63 males) aged 2 months to 12 years by urine culture and 99Tc-DMSA renal scan. A follow-up isotope scan was performed 4–6 months later to identify new renal scar formation. Vesicoureteral reflux (VUR) was examined by micturating cystourethrogram. Controls comprised 300 healthy children with no evidence of renal disease. Three single-nucleotide polymorphisms (SNPs) in the TGFβ-1 (−800 A/G, −509 C/T and 869 C/T) and four SNPs in the VEGF gene (−2578 C/A, −1154 G/A, −460 T/C and +405 G/C) were genotyped in all subjects. Results. Forty-six of the 104 patients developed renal parenchymal scarring (44.2%). VUR was found in 35.6%. The −509 T allele in the TGFβ-1 promoter was significantly more common in cases with renal scarring (51%) than in non-scarring patients (22.4%) and controls (23.6%) (both P < 0.0001). At the haplotype level, the GTC combination at −800/−509/+869 was strongly associated with renal scarring (P = 0.0002). VEGF−460 CC was more common in UTI cases with renal scarring than in non-scarring patients and controls (P = 0.03 and 0.001, respectively). Multiple logistic regression testing identified the presence of VUR (odds ratio 12.4, CI 3.8–40; P < 0.001) and the TGFβ-1 −509 T allele (OR 6.1, CI 2.4–15.5; P < 0.001) as independent risk factors for renal scarring after UTI. In contrast, age, gender and the type of underlying organism were not predictive of renal scarring. Conclusions. Activating variants in the TGFβ-1 and VEGF gene promoters are associated with post-UTI renal scar formation in children. The TGFβ-1 509T allele predicts renal scarring independent of VUR.</abstract><cop>Oxford</cop><pub>Oxford University Press</pub><pmid>19861314</pmid><doi>10.1093/ndt/gfp532</doi><tpages>7</tpages></addata></record> |
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| subjects | Alleles Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy Biological and medical sciences Case-Control Studies Child Child, Preschool Cicatrix - genetics Emergency and intensive care: renal failure. Dialysis management Female Genetic Predisposition to Disease - genetics Genotype haplotypes Haplotypes - genetics Humans Infant Intensive care medicine Kidney Logistic Models Male Medical sciences Nephrology. Urinary tract diseases Nephropathies. Renovascular diseases. Renal failure Polymorphism, Single Nucleotide - genetics polymorphisms renal Renal failure scarring TGFB1 Transforming Growth Factor beta1 - genetics Urinary Tract Infections - complications Vascular Endothelial Growth Factor A - genetics |
| title | Functional polymorphisms in transforming growth factor-beta-1 (TGFβ-1) and vascular endothelial growth factor (VEGF) genes modify risk of renal parenchymal scarring following childhood urinary tract infection |
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