Genetic associations in diabetic nephropathy: a meta-analysis
Aims/hypothesis This meta-analysis assessed the pooled effect of each genetic variant reproducibly associated with diabetic nephropathy. Methods PubMed, EMBASE and Web of Science were searched for articles assessing the association between genes and diabetic nephropathy. All genetic variants statist...
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| Veröffentlicht in: | Diabetologia 2011-03, Vol.54 (3), p.544-553 |
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| creator | Mooyaart, A. L Valk, E. J. J van Es, L. A Bruijn, J. A de Heer, E Freedman, B. I Dekkers, O. M Baelde, H. J |
| description | Aims/hypothesis This meta-analysis assessed the pooled effect of each genetic variant reproducibly associated with diabetic nephropathy. Methods PubMed, EMBASE and Web of Science were searched for articles assessing the association between genes and diabetic nephropathy. All genetic variants statistically associated with diabetic nephropathy in an initial study, then independently reproduced in at least one additional study, were selected. Subsequently, all studies assessing these variants were included. The association between these variants and diabetic nephropathy (defined as macroalbuminuria/proteinuria or end-stage renal disease [ESRD]) was calculated at the allele level and the main measure of effect was a pooled odds ratio. Pre-specified subgroup analyses were performed, stratifying for type 1/type 2 diabetes mellitus, proteinuria/ESRD and ethnic group. Results The literature search yielded 3,455 citations, of which 671 were genetic association studies investigating diabetic nephropathy. We identified 34 replicated genetic variants. Of these, 21 remained significantly associated with diabetic nephropathy in a random-effects meta-analysis. These variants were in or near the following genes: ACE, AKR1B1 (two variants), APOC1, APOE, EPO, NOS3 (two variants), HSPG2, VEGFA, FRMD3 (two variants), CARS (two variants), UNC13B, CPVL and CHN2, and GREM1, plus four variants not near genes. The odds ratios of associated genetic variants ranged from 0.48 to 1.70. Additional variants were detected in subgroup analyses: ELMO1 (Asians), CCR5 (Asians) and CNDP1 (type 2 diabetes). Conclusions/interpretation This meta-analysis found 24 genetic variants associated with diabetic nephropathy. The relative contribution and relevance of the identified genes in the pathogenesis of diabetic nephropathy should be the focus of future studies. |
| doi_str_mv | 10.1007/s00125-010-1996-1 |
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L ; Valk, E. J. J ; van Es, L. A ; Bruijn, J. A ; de Heer, E ; Freedman, B. I ; Dekkers, O. M ; Baelde, H. J</creator><creatorcontrib>Mooyaart, A. L ; Valk, E. J. J ; van Es, L. A ; Bruijn, J. A ; de Heer, E ; Freedman, B. I ; Dekkers, O. M ; Baelde, H. J</creatorcontrib><description>Aims/hypothesis This meta-analysis assessed the pooled effect of each genetic variant reproducibly associated with diabetic nephropathy. Methods PubMed, EMBASE and Web of Science were searched for articles assessing the association between genes and diabetic nephropathy. All genetic variants statistically associated with diabetic nephropathy in an initial study, then independently reproduced in at least one additional study, were selected. Subsequently, all studies assessing these variants were included. The association between these variants and diabetic nephropathy (defined as macroalbuminuria/proteinuria or end-stage renal disease [ESRD]) was calculated at the allele level and the main measure of effect was a pooled odds ratio. Pre-specified subgroup analyses were performed, stratifying for type 1/type 2 diabetes mellitus, proteinuria/ESRD and ethnic group. Results The literature search yielded 3,455 citations, of which 671 were genetic association studies investigating diabetic nephropathy. We identified 34 replicated genetic variants. Of these, 21 remained significantly associated with diabetic nephropathy in a random-effects meta-analysis. These variants were in or near the following genes: ACE, AKR1B1 (two variants), APOC1, APOE, EPO, NOS3 (two variants), HSPG2, VEGFA, FRMD3 (two variants), CARS (two variants), UNC13B, CPVL and CHN2, and GREM1, plus four variants not near genes. The odds ratios of associated genetic variants ranged from 0.48 to 1.70. Additional variants were detected in subgroup analyses: ELMO1 (Asians), CCR5 (Asians) and CNDP1 (type 2 diabetes). Conclusions/interpretation This meta-analysis found 24 genetic variants associated with diabetic nephropathy. The relative contribution and relevance of the identified genes in the pathogenesis of diabetic nephropathy should be the focus of future studies.</description><identifier>ISSN: 0012-186X</identifier><identifier>EISSN: 1432-0428</identifier><identifier>DOI: 10.1007/s00125-010-1996-1</identifier><identifier>PMID: 21127830</identifier><language>eng</language><publisher>Berlin/Heidelberg: Berlin/Heidelberg : Springer-Verlag</publisher><subject>Adaptor Proteins, Signal Transducing - genetics ; Apolipoprotein C-I - genetics ; Apolipoproteins E - genetics ; Associated diseases and complications ; Biological and medical sciences ; Carboxypeptidases - genetics ; Diabetes ; diabetes mellitus ; Diabetes. Impaired glucose tolerance ; Diabetic Nephropathies - genetics ; Diabetic nephropathy ; Dipeptidases - genetics ; Endocrine pancreas. Apud cells (diseases) ; Endocrinopathies ; Erythropoietin - genetics ; Etiopathogenesis. Screening. Investigations. Target tissue resistance ; Genetic association studies ; genetic polymorphism ; Genetic Variation - genetics ; Heparan Sulfate Proteoglycans - genetics ; Human Physiology ; Humans ; Intercellular Signaling Peptides and Proteins - genetics ; Internal Medicine ; Kidney diseases ; Kidneys ; Medical sciences ; Medicine ; Medicine & Public Health ; Meta-analysis ; Metabolic Diseases ; Nephrology ; Nephrology. Urinary tract diseases ; Nerve Tissue Proteins - genetics ; Nitric Oxide Synthase Type III - genetics ; Peptidyl-Dipeptidase A - genetics ; Polymorphism ; Polymorphism, Genetic - genetics ; Receptors, CCR5 - genetics ; Urinary system involvement in other diseases. Miscellaneous</subject><ispartof>Diabetologia, 2011-03, Vol.54 (3), p.544-553</ispartof><rights>The Author(s) 2010</rights><rights>2015 INIST-CNRS</rights><rights>Springer-Verlag 2011</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c620t-ef5ae45e903861a0287c74ffc670ca6f46caae27b8e45b9cfb21c9de2fb0373</citedby><cites>FETCH-LOGICAL-c620t-ef5ae45e903861a0287c74ffc670ca6f46caae27b8e45b9cfb21c9de2fb0373</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s00125-010-1996-1$$EPDF$$P50$$Gspringer$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s00125-010-1996-1$$EHTML$$P50$$Gspringer$$Hfree_for_read</linktohtml><link.rule.ids>230,314,776,780,881,27901,27902,41464,42533,51294</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=23864273$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/21127830$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Mooyaart, A. L</creatorcontrib><creatorcontrib>Valk, E. J. J</creatorcontrib><creatorcontrib>van Es, L. A</creatorcontrib><creatorcontrib>Bruijn, J. A</creatorcontrib><creatorcontrib>de Heer, E</creatorcontrib><creatorcontrib>Freedman, B. I</creatorcontrib><creatorcontrib>Dekkers, O. M</creatorcontrib><creatorcontrib>Baelde, H. J</creatorcontrib><title>Genetic associations in diabetic nephropathy: a meta-analysis</title><title>Diabetologia</title><addtitle>Diabetologia</addtitle><addtitle>Diabetologia</addtitle><description>Aims/hypothesis This meta-analysis assessed the pooled effect of each genetic variant reproducibly associated with diabetic nephropathy. Methods PubMed, EMBASE and Web of Science were searched for articles assessing the association between genes and diabetic nephropathy. All genetic variants statistically associated with diabetic nephropathy in an initial study, then independently reproduced in at least one additional study, were selected. Subsequently, all studies assessing these variants were included. The association between these variants and diabetic nephropathy (defined as macroalbuminuria/proteinuria or end-stage renal disease [ESRD]) was calculated at the allele level and the main measure of effect was a pooled odds ratio. Pre-specified subgroup analyses were performed, stratifying for type 1/type 2 diabetes mellitus, proteinuria/ESRD and ethnic group. Results The literature search yielded 3,455 citations, of which 671 were genetic association studies investigating diabetic nephropathy. We identified 34 replicated genetic variants. Of these, 21 remained significantly associated with diabetic nephropathy in a random-effects meta-analysis. These variants were in or near the following genes: ACE, AKR1B1 (two variants), APOC1, APOE, EPO, NOS3 (two variants), HSPG2, VEGFA, FRMD3 (two variants), CARS (two variants), UNC13B, CPVL and CHN2, and GREM1, plus four variants not near genes. The odds ratios of associated genetic variants ranged from 0.48 to 1.70. Additional variants were detected in subgroup analyses: ELMO1 (Asians), CCR5 (Asians) and CNDP1 (type 2 diabetes). Conclusions/interpretation This meta-analysis found 24 genetic variants associated with diabetic nephropathy. The relative contribution and relevance of the identified genes in the pathogenesis of diabetic nephropathy should be the focus of future studies.</description><subject>Adaptor Proteins, Signal Transducing - genetics</subject><subject>Apolipoprotein C-I - genetics</subject><subject>Apolipoproteins E - genetics</subject><subject>Associated diseases and complications</subject><subject>Biological and medical sciences</subject><subject>Carboxypeptidases - genetics</subject><subject>Diabetes</subject><subject>diabetes mellitus</subject><subject>Diabetes. Impaired glucose tolerance</subject><subject>Diabetic Nephropathies - genetics</subject><subject>Diabetic nephropathy</subject><subject>Dipeptidases - genetics</subject><subject>Endocrine pancreas. Apud cells (diseases)</subject><subject>Endocrinopathies</subject><subject>Erythropoietin - genetics</subject><subject>Etiopathogenesis. Screening. Investigations. Target tissue resistance</subject><subject>Genetic association studies</subject><subject>genetic polymorphism</subject><subject>Genetic Variation - genetics</subject><subject>Heparan Sulfate Proteoglycans - genetics</subject><subject>Human Physiology</subject><subject>Humans</subject><subject>Intercellular Signaling Peptides and Proteins - genetics</subject><subject>Internal Medicine</subject><subject>Kidney diseases</subject><subject>Kidneys</subject><subject>Medical sciences</subject><subject>Medicine</subject><subject>Medicine & Public Health</subject><subject>Meta-analysis</subject><subject>Metabolic Diseases</subject><subject>Nephrology</subject><subject>Nephrology. Urinary tract diseases</subject><subject>Nerve Tissue Proteins - genetics</subject><subject>Nitric Oxide Synthase Type III - genetics</subject><subject>Peptidyl-Dipeptidase A - genetics</subject><subject>Polymorphism</subject><subject>Polymorphism, Genetic - genetics</subject><subject>Receptors, CCR5 - genetics</subject><subject>Urinary system involvement in other diseases. 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L ; Valk, E. J. J ; van Es, L. A ; Bruijn, J. A ; de Heer, E ; Freedman, B. I ; Dekkers, O. M ; Baelde, H. J</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c620t-ef5ae45e903861a0287c74ffc670ca6f46caae27b8e45b9cfb21c9de2fb0373</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2011</creationdate><topic>Adaptor Proteins, Signal Transducing - genetics</topic><topic>Apolipoprotein C-I - genetics</topic><topic>Apolipoproteins E - genetics</topic><topic>Associated diseases and complications</topic><topic>Biological and medical sciences</topic><topic>Carboxypeptidases - genetics</topic><topic>Diabetes</topic><topic>diabetes mellitus</topic><topic>Diabetes. Impaired glucose tolerance</topic><topic>Diabetic Nephropathies - genetics</topic><topic>Diabetic nephropathy</topic><topic>Dipeptidases - genetics</topic><topic>Endocrine pancreas. Apud cells (diseases)</topic><topic>Endocrinopathies</topic><topic>Erythropoietin - genetics</topic><topic>Etiopathogenesis. Screening. Investigations. Target tissue resistance</topic><topic>Genetic association studies</topic><topic>genetic polymorphism</topic><topic>Genetic Variation - genetics</topic><topic>Heparan Sulfate Proteoglycans - genetics</topic><topic>Human Physiology</topic><topic>Humans</topic><topic>Intercellular Signaling Peptides and Proteins - genetics</topic><topic>Internal Medicine</topic><topic>Kidney diseases</topic><topic>Kidneys</topic><topic>Medical sciences</topic><topic>Medicine</topic><topic>Medicine & Public Health</topic><topic>Meta-analysis</topic><topic>Metabolic Diseases</topic><topic>Nephrology</topic><topic>Nephrology. Urinary tract diseases</topic><topic>Nerve Tissue Proteins - genetics</topic><topic>Nitric Oxide Synthase Type III - genetics</topic><topic>Peptidyl-Dipeptidase A - genetics</topic><topic>Polymorphism</topic><topic>Polymorphism, Genetic - genetics</topic><topic>Receptors, CCR5 - genetics</topic><topic>Urinary system involvement in other diseases. Miscellaneous</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Mooyaart, A. L</creatorcontrib><creatorcontrib>Valk, E. J. J</creatorcontrib><creatorcontrib>van Es, L. A</creatorcontrib><creatorcontrib>Bruijn, J. A</creatorcontrib><creatorcontrib>de Heer, E</creatorcontrib><creatorcontrib>Freedman, B. I</creatorcontrib><creatorcontrib>Dekkers, O. M</creatorcontrib><creatorcontrib>Baelde, H. 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L</au><au>Valk, E. J. J</au><au>van Es, L. A</au><au>Bruijn, J. A</au><au>de Heer, E</au><au>Freedman, B. I</au><au>Dekkers, O. M</au><au>Baelde, H. J</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Genetic associations in diabetic nephropathy: a meta-analysis</atitle><jtitle>Diabetologia</jtitle><stitle>Diabetologia</stitle><addtitle>Diabetologia</addtitle><date>2011-03-01</date><risdate>2011</risdate><volume>54</volume><issue>3</issue><spage>544</spage><epage>553</epage><pages>544-553</pages><issn>0012-186X</issn><eissn>1432-0428</eissn><abstract>Aims/hypothesis This meta-analysis assessed the pooled effect of each genetic variant reproducibly associated with diabetic nephropathy. Methods PubMed, EMBASE and Web of Science were searched for articles assessing the association between genes and diabetic nephropathy. All genetic variants statistically associated with diabetic nephropathy in an initial study, then independently reproduced in at least one additional study, were selected. Subsequently, all studies assessing these variants were included. The association between these variants and diabetic nephropathy (defined as macroalbuminuria/proteinuria or end-stage renal disease [ESRD]) was calculated at the allele level and the main measure of effect was a pooled odds ratio. Pre-specified subgroup analyses were performed, stratifying for type 1/type 2 diabetes mellitus, proteinuria/ESRD and ethnic group. Results The literature search yielded 3,455 citations, of which 671 were genetic association studies investigating diabetic nephropathy. We identified 34 replicated genetic variants. Of these, 21 remained significantly associated with diabetic nephropathy in a random-effects meta-analysis. These variants were in or near the following genes: ACE, AKR1B1 (two variants), APOC1, APOE, EPO, NOS3 (two variants), HSPG2, VEGFA, FRMD3 (two variants), CARS (two variants), UNC13B, CPVL and CHN2, and GREM1, plus four variants not near genes. The odds ratios of associated genetic variants ranged from 0.48 to 1.70. Additional variants were detected in subgroup analyses: ELMO1 (Asians), CCR5 (Asians) and CNDP1 (type 2 diabetes). Conclusions/interpretation This meta-analysis found 24 genetic variants associated with diabetic nephropathy. The relative contribution and relevance of the identified genes in the pathogenesis of diabetic nephropathy should be the focus of future studies.</abstract><cop>Berlin/Heidelberg</cop><pub>Berlin/Heidelberg : Springer-Verlag</pub><pmid>21127830</pmid><doi>10.1007/s00125-010-1996-1</doi><tpages>10</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Adaptor Proteins, Signal Transducing - genetics Apolipoprotein C-I - genetics Apolipoproteins E - genetics Associated diseases and complications Biological and medical sciences Carboxypeptidases - genetics Diabetes diabetes mellitus Diabetes. Impaired glucose tolerance Diabetic Nephropathies - genetics Diabetic nephropathy Dipeptidases - genetics Endocrine pancreas. Apud cells (diseases) Endocrinopathies Erythropoietin - genetics Etiopathogenesis. Screening. Investigations. Target tissue resistance Genetic association studies genetic polymorphism Genetic Variation - genetics Heparan Sulfate Proteoglycans - genetics Human Physiology Humans Intercellular Signaling Peptides and Proteins - genetics Internal Medicine Kidney diseases Kidneys Medical sciences Medicine Medicine & Public Health Meta-analysis Metabolic Diseases Nephrology Nephrology. Urinary tract diseases Nerve Tissue Proteins - genetics Nitric Oxide Synthase Type III - genetics Peptidyl-Dipeptidase A - genetics Polymorphism Polymorphism, Genetic - genetics Receptors, CCR5 - genetics Urinary system involvement in other diseases. Miscellaneous |
| title | Genetic associations in diabetic nephropathy: a meta-analysis |
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