A renal genetic risk score (GRS) is associated with kidney dysfunction in people with type 2 diabetes
This study aims to investigate whether renal and cardiovascular phenotypes in Italian patients with type 2 diabetes (T2D) could be influenced by a number of disease risk SNPs recently found in genome-wide association studies (GWAS). In 1591 Italian subjects with T2D: (1) 47 SNPs associated to kidney...
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| Veröffentlicht in: | Diabetes research and clinical practice 2018-10, Vol.144, p.137-143 |
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| creator | Zusi, Chiara Trombetta, Maddalena Bonetti, Sara Dauriz, Marco Boselli, Maria L. Trabetti, Elisabetta Malerba, Giovanni Penno, Giuseppe Zoppini, Giacomo Bonora, Enzo Solini, Anna Bonadonna, Riccardo C. |
| description | This study aims to investigate whether renal and cardiovascular phenotypes in Italian patients with type 2 diabetes (T2D) could be influenced by a number of disease risk SNPs recently found in genome-wide association studies (GWAS).
In 1591 Italian subjects with T2D: (1) 47 SNPs associated to kidney function and/or chronic kidney disease (CKD) and 49 SNPs associated to cardiovascular disease (CVD) risk were genotyped; (2) urinary albumin/creatinine (A/C) ratio, glomerular filtration rate (eGFR) and lipid profile were assessed; (3) a standard electrocardiogram was performed; (4) two genotype risk scores (GRS) were computed (a renal GRS calculated selecting 39 SNPs associated with intermediate traits of kidney damage and a cardiovascular GRS determined selecting 42 SNPs associated to CVD risk phenotypes). After correction for multiple comparisons, the renal GRS was not associated to A/C ratio (p = 0.33), but it was significantly related to decreased eGFR (p = 0.005). No association between the cardiovascular GRS and electrocardiogram was detected.
Thus, in Italian patients with T2D a renal GRS might predict the decline in glomerular function, suggesting that the clock of diabetes associated CKD starts ticking long before hyperglycemia. Our data support the feasibility of gene-based prediction of complications in people with T2D. |
| doi_str_mv | 10.1016/j.diabres.2018.08.013 |
| format | Article |
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In 1591 Italian subjects with T2D: (1) 47 SNPs associated to kidney function and/or chronic kidney disease (CKD) and 49 SNPs associated to cardiovascular disease (CVD) risk were genotyped; (2) urinary albumin/creatinine (A/C) ratio, glomerular filtration rate (eGFR) and lipid profile were assessed; (3) a standard electrocardiogram was performed; (4) two genotype risk scores (GRS) were computed (a renal GRS calculated selecting 39 SNPs associated with intermediate traits of kidney damage and a cardiovascular GRS determined selecting 42 SNPs associated to CVD risk phenotypes). After correction for multiple comparisons, the renal GRS was not associated to A/C ratio (p = 0.33), but it was significantly related to decreased eGFR (p = 0.005). No association between the cardiovascular GRS and electrocardiogram was detected.
Thus, in Italian patients with T2D a renal GRS might predict the decline in glomerular function, suggesting that the clock of diabetes associated CKD starts ticking long before hyperglycemia. Our data support the feasibility of gene-based prediction of complications in people with T2D.</description><identifier>ISSN: 0168-8227</identifier><identifier>EISSN: 1872-8227</identifier><identifier>DOI: 10.1016/j.diabres.2018.08.013</identifier><identifier>PMID: 30153470</identifier><language>eng</language><publisher>Ireland: Elsevier B.V</publisher><subject>Aged ; Diabetes Mellitus, Type 2 - complications ; Diabetes Mellitus, Type 2 - genetics ; Female ; Genetic Markers ; Genetic Predisposition to Disease ; Genome-Wide Association Study ; Genotype ; Glomerular Filtration Rate ; Humans ; Male ; Middle Aged ; Polymorphism, Single Nucleotide ; Renal Insufficiency, Chronic - etiology ; Renal Insufficiency, Chronic - pathology ; Risk Assessment ; Risk Factors</subject><ispartof>Diabetes research and clinical practice, 2018-10, Vol.144, p.137-143</ispartof><rights>2018 Elsevier B.V.</rights><rights>Copyright © 2018 Elsevier B.V. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c365t-98b6fc72e297a4848d4ae4d898daf06ed549725f6ba0107e5fa3b049792f4b973</citedby><cites>FETCH-LOGICAL-c365t-98b6fc72e297a4848d4ae4d898daf06ed549725f6ba0107e5fa3b049792f4b973</cites><orcidid>0000-0002-2834-4847</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0168822718304297$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3537,27901,27902,65306</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/30153470$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Zusi, Chiara</creatorcontrib><creatorcontrib>Trombetta, Maddalena</creatorcontrib><creatorcontrib>Bonetti, Sara</creatorcontrib><creatorcontrib>Dauriz, Marco</creatorcontrib><creatorcontrib>Boselli, Maria L.</creatorcontrib><creatorcontrib>Trabetti, Elisabetta</creatorcontrib><creatorcontrib>Malerba, Giovanni</creatorcontrib><creatorcontrib>Penno, Giuseppe</creatorcontrib><creatorcontrib>Zoppini, Giacomo</creatorcontrib><creatorcontrib>Bonora, Enzo</creatorcontrib><creatorcontrib>Solini, Anna</creatorcontrib><creatorcontrib>Bonadonna, Riccardo C.</creatorcontrib><title>A renal genetic risk score (GRS) is associated with kidney dysfunction in people with type 2 diabetes</title><title>Diabetes research and clinical practice</title><addtitle>Diabetes Res Clin Pract</addtitle><description>This study aims to investigate whether renal and cardiovascular phenotypes in Italian patients with type 2 diabetes (T2D) could be influenced by a number of disease risk SNPs recently found in genome-wide association studies (GWAS).
In 1591 Italian subjects with T2D: (1) 47 SNPs associated to kidney function and/or chronic kidney disease (CKD) and 49 SNPs associated to cardiovascular disease (CVD) risk were genotyped; (2) urinary albumin/creatinine (A/C) ratio, glomerular filtration rate (eGFR) and lipid profile were assessed; (3) a standard electrocardiogram was performed; (4) two genotype risk scores (GRS) were computed (a renal GRS calculated selecting 39 SNPs associated with intermediate traits of kidney damage and a cardiovascular GRS determined selecting 42 SNPs associated to CVD risk phenotypes). After correction for multiple comparisons, the renal GRS was not associated to A/C ratio (p = 0.33), but it was significantly related to decreased eGFR (p = 0.005). No association between the cardiovascular GRS and electrocardiogram was detected.
Thus, in Italian patients with T2D a renal GRS might predict the decline in glomerular function, suggesting that the clock of diabetes associated CKD starts ticking long before hyperglycemia. Our data support the feasibility of gene-based prediction of complications in people with T2D.</description><subject>Aged</subject><subject>Diabetes Mellitus, Type 2 - complications</subject><subject>Diabetes Mellitus, Type 2 - genetics</subject><subject>Female</subject><subject>Genetic Markers</subject><subject>Genetic Predisposition to Disease</subject><subject>Genome-Wide Association Study</subject><subject>Genotype</subject><subject>Glomerular Filtration Rate</subject><subject>Humans</subject><subject>Male</subject><subject>Middle Aged</subject><subject>Polymorphism, Single Nucleotide</subject><subject>Renal Insufficiency, Chronic - etiology</subject><subject>Renal Insufficiency, Chronic - pathology</subject><subject>Risk Assessment</subject><subject>Risk Factors</subject><issn>0168-8227</issn><issn>1872-8227</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2018</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkE1vFDEMhiMEokvLT2iVYzns4nzNZE6oqkpBqoQE9BxlEk-b7ezMNM6C9t8zyy69IlmyZT32a7-MnQtYCRDVx_UqJt9mpJUEYVcwh1Cv2ELYWi6tlPVrtpg5-7c-Ye-I1gBQKW3eshMFwihdw4LhFc84-J4_4IAlBZ4TPXEKY0Z-efv9xweeiHuiMSRfMPLfqTzypxQH3PG4o247hJLGgaeBTzhOPR6IspuQS74_EQvSGXvT-Z7w_TGfsvvPNz-vvyzvvt1-vb66WwZVmbJsbFt1oZYom9prq23UHnW0jY2-gwqj0U0tTVe1HgTUaDqvWph7jex029TqlF0e9k55fN4iFbdJFLDv_YDjlpyEpjJGNaBn1BzQkEeijJ2bctr4vHMC3N5ht3ZHh93eYQdzCDXPXRwltu0G48vUP0tn4NMBwPnRXwmzo5BwCBhTxlBcHNN_JP4Ail6O2g</recordid><startdate>201810</startdate><enddate>201810</enddate><creator>Zusi, Chiara</creator><creator>Trombetta, Maddalena</creator><creator>Bonetti, Sara</creator><creator>Dauriz, Marco</creator><creator>Boselli, Maria L.</creator><creator>Trabetti, Elisabetta</creator><creator>Malerba, Giovanni</creator><creator>Penno, Giuseppe</creator><creator>Zoppini, Giacomo</creator><creator>Bonora, Enzo</creator><creator>Solini, Anna</creator><creator>Bonadonna, Riccardo C.</creator><general>Elsevier B.V</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>7X8</scope><orcidid>https://orcid.org/0000-0002-2834-4847</orcidid></search><sort><creationdate>201810</creationdate><title>A renal genetic risk score (GRS) is associated with kidney dysfunction in people with type 2 diabetes</title><author>Zusi, Chiara ; Trombetta, Maddalena ; Bonetti, Sara ; Dauriz, Marco ; Boselli, Maria L. ; Trabetti, Elisabetta ; Malerba, Giovanni ; Penno, Giuseppe ; Zoppini, Giacomo ; Bonora, Enzo ; Solini, Anna ; Bonadonna, Riccardo C.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c365t-98b6fc72e297a4848d4ae4d898daf06ed549725f6ba0107e5fa3b049792f4b973</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2018</creationdate><topic>Aged</topic><topic>Diabetes Mellitus, Type 2 - complications</topic><topic>Diabetes Mellitus, Type 2 - genetics</topic><topic>Female</topic><topic>Genetic Markers</topic><topic>Genetic Predisposition to Disease</topic><topic>Genome-Wide Association Study</topic><topic>Genotype</topic><topic>Glomerular Filtration Rate</topic><topic>Humans</topic><topic>Male</topic><topic>Middle Aged</topic><topic>Polymorphism, Single Nucleotide</topic><topic>Renal Insufficiency, Chronic - etiology</topic><topic>Renal Insufficiency, Chronic - pathology</topic><topic>Risk Assessment</topic><topic>Risk Factors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Zusi, Chiara</creatorcontrib><creatorcontrib>Trombetta, Maddalena</creatorcontrib><creatorcontrib>Bonetti, Sara</creatorcontrib><creatorcontrib>Dauriz, Marco</creatorcontrib><creatorcontrib>Boselli, Maria L.</creatorcontrib><creatorcontrib>Trabetti, Elisabetta</creatorcontrib><creatorcontrib>Malerba, Giovanni</creatorcontrib><creatorcontrib>Penno, Giuseppe</creatorcontrib><creatorcontrib>Zoppini, Giacomo</creatorcontrib><creatorcontrib>Bonora, Enzo</creatorcontrib><creatorcontrib>Solini, Anna</creatorcontrib><creatorcontrib>Bonadonna, Riccardo C.</creatorcontrib><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>Diabetes research and clinical practice</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Zusi, Chiara</au><au>Trombetta, Maddalena</au><au>Bonetti, Sara</au><au>Dauriz, Marco</au><au>Boselli, Maria L.</au><au>Trabetti, Elisabetta</au><au>Malerba, Giovanni</au><au>Penno, Giuseppe</au><au>Zoppini, Giacomo</au><au>Bonora, Enzo</au><au>Solini, Anna</au><au>Bonadonna, Riccardo C.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>A renal genetic risk score (GRS) is associated with kidney dysfunction in people with type 2 diabetes</atitle><jtitle>Diabetes research and clinical practice</jtitle><addtitle>Diabetes Res Clin Pract</addtitle><date>2018-10</date><risdate>2018</risdate><volume>144</volume><spage>137</spage><epage>143</epage><pages>137-143</pages><issn>0168-8227</issn><eissn>1872-8227</eissn><abstract>This study aims to investigate whether renal and cardiovascular phenotypes in Italian patients with type 2 diabetes (T2D) could be influenced by a number of disease risk SNPs recently found in genome-wide association studies (GWAS).
In 1591 Italian subjects with T2D: (1) 47 SNPs associated to kidney function and/or chronic kidney disease (CKD) and 49 SNPs associated to cardiovascular disease (CVD) risk were genotyped; (2) urinary albumin/creatinine (A/C) ratio, glomerular filtration rate (eGFR) and lipid profile were assessed; (3) a standard electrocardiogram was performed; (4) two genotype risk scores (GRS) were computed (a renal GRS calculated selecting 39 SNPs associated with intermediate traits of kidney damage and a cardiovascular GRS determined selecting 42 SNPs associated to CVD risk phenotypes). After correction for multiple comparisons, the renal GRS was not associated to A/C ratio (p = 0.33), but it was significantly related to decreased eGFR (p = 0.005). No association between the cardiovascular GRS and electrocardiogram was detected.
Thus, in Italian patients with T2D a renal GRS might predict the decline in glomerular function, suggesting that the clock of diabetes associated CKD starts ticking long before hyperglycemia. Our data support the feasibility of gene-based prediction of complications in people with T2D.</abstract><cop>Ireland</cop><pub>Elsevier B.V</pub><pmid>30153470</pmid><doi>10.1016/j.diabres.2018.08.013</doi><tpages>7</tpages><orcidid>https://orcid.org/0000-0002-2834-4847</orcidid></addata></record> |
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| subjects | Aged Diabetes Mellitus, Type 2 - complications Diabetes Mellitus, Type 2 - genetics Female Genetic Markers Genetic Predisposition to Disease Genome-Wide Association Study Genotype Glomerular Filtration Rate Humans Male Middle Aged Polymorphism, Single Nucleotide Renal Insufficiency, Chronic - etiology Renal Insufficiency, Chronic - pathology Risk Assessment Risk Factors |
| title | A renal genetic risk score (GRS) is associated with kidney dysfunction in people with type 2 diabetes |
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