Nodular glomerulosclerosis and renin angiotensin system in Chinese patients with type 2 diabetes
Diabetic nephropathy (DN) is a multifactorial and polygenic disease with nodular glomerulosclerosis (NGS) pathognomonic for diabetes and hypertension. Patients with type 2 diabetes and hypertension have characteristic renin-angiotensin system (RAS) gene polymorphisms. In this retrospective cohort st...
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| Veröffentlicht in: | Molecular and cellular endocrinology 2016-05, Vol.427, p.92-100 |
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| creator | Wang, Min Zhang, Xiaoxi Song, Xinnan Zou, Xia Wu, Weijie Wang, Yanchao Lin, Bingjie Li, Rong Hu, Fang Zhao, Hailu |
| description | Diabetic nephropathy (DN) is a multifactorial and polygenic disease with nodular glomerulosclerosis (NGS) pathognomonic for diabetes and hypertension. Patients with type 2 diabetes and hypertension have characteristic renin-angiotensin system (RAS) gene polymorphisms.
In this retrospective cohort study, we correlated the presence of NGS with renal function, angiotensin-converting enzyme (ACE) genotypes (DD, DI, and II), angiotensinogen (AGT) genotypes (MM, MT, and TT) and immunohistochemical staining characteristics of RAS components in 847 patients and 172 consecutive autopsy cases with type 2 diabetes. T allele of AGT was associated with macroalbuminuria (P = 0.040). Multitude regression analysis revealed ACE insertion (I)/deletion (D) polymorphism as an independent determinant for estimated glomerular filtration rate (eGFR) less than 60 mL min−1·1.73 m−2 (DD carriers: odds ratio [OR] = 3.46, 95% confidence interval [CI] = 1.08–11.07; DI carriers: OR = 3.51, 95% CI = 1.63–7.56). A significant association between NGS and eGFR less than 60 mL min−1·1.73 m−2 also persisted after adjusting for nonlinear relationship (P |
| doi_str_mv | 10.1016/j.mce.2016.03.008 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_1816024528</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><els_id>S0303720716300569</els_id><sourcerecordid>1816024528</sourcerecordid><originalsourceid>FETCH-LOGICAL-c386t-7b3ec11cd3672e7266efaa982fcc7437e1a888ef4a35d99410f057dfb5df7e343</originalsourceid><addsrcrecordid>eNp9kLlOLDEQRS0EgmH5AJInhyTdeOlpu0WERmwSggRi47GrwaNe5rncoPl7jAYIieoEt650DyGnnJWc8fp8VfYOSpGxZLJkTO-QGddKFJrN1S6ZMclkoQRTB-QQccUYU3Oh98mBqBslRSNn5OVh9FNnI33txh7i1I3oOogjBqR28DTCEIZMr2FMMGBm3GCCnmZavIUBEOjapgBDQvoR0htNmzVQQX2wS0iAx2SvtR3Cyfc9Is_XV0-L2-L-8eZucXlfOKnrVKilBMe587JWApSoa2itbbRonVOVVMCt1hraysq5b5qKszZv9O1y7lsFspJH5Gzbu47j_wkwmT6gg66zA4wTGq55zUSV9-co30Zd3okRWrOOobdxYzgzX2LNymSx5kusYdJksfnn33f9tOzB_378mMyBi20A8sj3ANGgy1Yc-BDBJePH8Ef9J-B2imw</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1816024528</pqid></control><display><type>article</type><title>Nodular glomerulosclerosis and renin angiotensin system in Chinese patients with type 2 diabetes</title><source>MEDLINE</source><source>Access via ScienceDirect (Elsevier)</source><creator>Wang, Min ; Zhang, Xiaoxi ; Song, Xinnan ; Zou, Xia ; Wu, Weijie ; Wang, Yanchao ; Lin, Bingjie ; Li, Rong ; Hu, Fang ; Zhao, Hailu</creator><creatorcontrib>Wang, Min ; Zhang, Xiaoxi ; Song, Xinnan ; Zou, Xia ; Wu, Weijie ; Wang, Yanchao ; Lin, Bingjie ; Li, Rong ; Hu, Fang ; Zhao, Hailu</creatorcontrib><description>Diabetic nephropathy (DN) is a multifactorial and polygenic disease with nodular glomerulosclerosis (NGS) pathognomonic for diabetes and hypertension. Patients with type 2 diabetes and hypertension have characteristic renin-angiotensin system (RAS) gene polymorphisms.
In this retrospective cohort study, we correlated the presence of NGS with renal function, angiotensin-converting enzyme (ACE) genotypes (DD, DI, and II), angiotensinogen (AGT) genotypes (MM, MT, and TT) and immunohistochemical staining characteristics of RAS components in 847 patients and 172 consecutive autopsy cases with type 2 diabetes. T allele of AGT was associated with macroalbuminuria (P = 0.040). Multitude regression analysis revealed ACE insertion (I)/deletion (D) polymorphism as an independent determinant for estimated glomerular filtration rate (eGFR) less than 60 mL min−1·1.73 m−2 (DD carriers: odds ratio [OR] = 3.46, 95% confidence interval [CI] = 1.08–11.07; DI carriers: OR = 3.51, 95% CI = 1.63–7.56). A significant association between NGS and eGFR less than 60 mL min−1·1.73 m−2 also persisted after adjusting for nonlinear relationship (P < 0.001). In NGS patients, immunoreactivity of angiotensin I converting enzyme 2 (ACE2) significantly decreased in glomeruli with mesangial nodules compared with glomeruli without the mesangial nodules.
These data suggest associations of ACE D allele with glomerular filtration impairment, and NGS with glomerular ACE2 down-regulation and reduced glomerular filtration in Chinese patients with type 2 diabetes.
•This study reveals an association of RAS components and NGS in patients and autopsy cases with type 2 diabetes.•The patients with ACE D or AGT T alleles might have reduced eGFR and macroalbuminuria.•Difference in the immunoreactivity of ACE2 may contribute to the development of nodular glomerulosclerosis.</description><identifier>ISSN: 0303-7207</identifier><identifier>EISSN: 1872-8057</identifier><identifier>DOI: 10.1016/j.mce.2016.03.008</identifier><identifier>PMID: 26973293</identifier><language>eng</language><publisher>Ireland: Elsevier Ireland Ltd</publisher><subject>Angiotensin I converting enzyme 2 ; Asian Continental Ancestry Group - genetics ; Carriers ; China ; Cohort Studies ; Diabetes ; Diabetes Mellitus, Type 2 - genetics ; Diabetic Nephropathies - genetics ; Diabetic Nephropathies - pathology ; Enzymes ; Female ; Filtration ; Genetic Association Studies ; Genotype ; Glomerular Filtration Rate - genetics ; Humans ; Hypertension ; Hypertension - complications ; Immunophenotyping ; Lipids - blood ; Male ; Middle Aged ; Nodular glomerulosclerosis ; Nodules ; Patients ; Polymorphism ; Polymorphism, Genetic ; Proteinuria - genetics ; Renin-angiotensin system ; Renin-Angiotensin System - genetics ; Renin-Angiotensin System - immunology ; Retrospective Studies ; Type 2 diabetes</subject><ispartof>Molecular and cellular endocrinology, 2016-05, Vol.427, p.92-100</ispartof><rights>2016 Elsevier Ireland Ltd</rights><rights>Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c386t-7b3ec11cd3672e7266efaa982fcc7437e1a888ef4a35d99410f057dfb5df7e343</citedby><cites>FETCH-LOGICAL-c386t-7b3ec11cd3672e7266efaa982fcc7437e1a888ef4a35d99410f057dfb5df7e343</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.mce.2016.03.008$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,780,784,3550,27924,27925,45995</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/26973293$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Wang, Min</creatorcontrib><creatorcontrib>Zhang, Xiaoxi</creatorcontrib><creatorcontrib>Song, Xinnan</creatorcontrib><creatorcontrib>Zou, Xia</creatorcontrib><creatorcontrib>Wu, Weijie</creatorcontrib><creatorcontrib>Wang, Yanchao</creatorcontrib><creatorcontrib>Lin, Bingjie</creatorcontrib><creatorcontrib>Li, Rong</creatorcontrib><creatorcontrib>Hu, Fang</creatorcontrib><creatorcontrib>Zhao, Hailu</creatorcontrib><title>Nodular glomerulosclerosis and renin angiotensin system in Chinese patients with type 2 diabetes</title><title>Molecular and cellular endocrinology</title><addtitle>Mol Cell Endocrinol</addtitle><description>Diabetic nephropathy (DN) is a multifactorial and polygenic disease with nodular glomerulosclerosis (NGS) pathognomonic for diabetes and hypertension. Patients with type 2 diabetes and hypertension have characteristic renin-angiotensin system (RAS) gene polymorphisms.
In this retrospective cohort study, we correlated the presence of NGS with renal function, angiotensin-converting enzyme (ACE) genotypes (DD, DI, and II), angiotensinogen (AGT) genotypes (MM, MT, and TT) and immunohistochemical staining characteristics of RAS components in 847 patients and 172 consecutive autopsy cases with type 2 diabetes. T allele of AGT was associated with macroalbuminuria (P = 0.040). Multitude regression analysis revealed ACE insertion (I)/deletion (D) polymorphism as an independent determinant for estimated glomerular filtration rate (eGFR) less than 60 mL min−1·1.73 m−2 (DD carriers: odds ratio [OR] = 3.46, 95% confidence interval [CI] = 1.08–11.07; DI carriers: OR = 3.51, 95% CI = 1.63–7.56). A significant association between NGS and eGFR less than 60 mL min−1·1.73 m−2 also persisted after adjusting for nonlinear relationship (P < 0.001). In NGS patients, immunoreactivity of angiotensin I converting enzyme 2 (ACE2) significantly decreased in glomeruli with mesangial nodules compared with glomeruli without the mesangial nodules.
These data suggest associations of ACE D allele with glomerular filtration impairment, and NGS with glomerular ACE2 down-regulation and reduced glomerular filtration in Chinese patients with type 2 diabetes.
•This study reveals an association of RAS components and NGS in patients and autopsy cases with type 2 diabetes.•The patients with ACE D or AGT T alleles might have reduced eGFR and macroalbuminuria.•Difference in the immunoreactivity of ACE2 may contribute to the development of nodular glomerulosclerosis.</description><subject>Angiotensin I converting enzyme 2</subject><subject>Asian Continental Ancestry Group - genetics</subject><subject>Carriers</subject><subject>China</subject><subject>Cohort Studies</subject><subject>Diabetes</subject><subject>Diabetes Mellitus, Type 2 - genetics</subject><subject>Diabetic Nephropathies - genetics</subject><subject>Diabetic Nephropathies - pathology</subject><subject>Enzymes</subject><subject>Female</subject><subject>Filtration</subject><subject>Genetic Association Studies</subject><subject>Genotype</subject><subject>Glomerular Filtration Rate - genetics</subject><subject>Humans</subject><subject>Hypertension</subject><subject>Hypertension - complications</subject><subject>Immunophenotyping</subject><subject>Lipids - blood</subject><subject>Male</subject><subject>Middle Aged</subject><subject>Nodular glomerulosclerosis</subject><subject>Nodules</subject><subject>Patients</subject><subject>Polymorphism</subject><subject>Polymorphism, Genetic</subject><subject>Proteinuria - genetics</subject><subject>Renin-angiotensin system</subject><subject>Renin-Angiotensin System - genetics</subject><subject>Renin-Angiotensin System - immunology</subject><subject>Retrospective Studies</subject><subject>Type 2 diabetes</subject><issn>0303-7207</issn><issn>1872-8057</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2016</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kLlOLDEQRS0EgmH5AJInhyTdeOlpu0WERmwSggRi47GrwaNe5rncoPl7jAYIieoEt650DyGnnJWc8fp8VfYOSpGxZLJkTO-QGddKFJrN1S6ZMclkoQRTB-QQccUYU3Oh98mBqBslRSNn5OVh9FNnI33txh7i1I3oOogjBqR28DTCEIZMr2FMMGBm3GCCnmZavIUBEOjapgBDQvoR0htNmzVQQX2wS0iAx2SvtR3Cyfc9Is_XV0-L2-L-8eZucXlfOKnrVKilBMe587JWApSoa2itbbRonVOVVMCt1hraysq5b5qKszZv9O1y7lsFspJH5Gzbu47j_wkwmT6gg66zA4wTGq55zUSV9-co30Zd3okRWrOOobdxYzgzX2LNymSx5kusYdJksfnn33f9tOzB_378mMyBi20A8sj3ANGgy1Yc-BDBJePH8Ef9J-B2imw</recordid><startdate>20160515</startdate><enddate>20160515</enddate><creator>Wang, Min</creator><creator>Zhang, Xiaoxi</creator><creator>Song, Xinnan</creator><creator>Zou, Xia</creator><creator>Wu, Weijie</creator><creator>Wang, Yanchao</creator><creator>Lin, Bingjie</creator><creator>Li, Rong</creator><creator>Hu, Fang</creator><creator>Zhao, Hailu</creator><general>Elsevier Ireland Ltd</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>7U5</scope><scope>8FD</scope><scope>L7M</scope></search><sort><creationdate>20160515</creationdate><title>Nodular glomerulosclerosis and renin angiotensin system in Chinese patients with type 2 diabetes</title><author>Wang, Min ; Zhang, Xiaoxi ; Song, Xinnan ; Zou, Xia ; Wu, Weijie ; Wang, Yanchao ; Lin, Bingjie ; Li, Rong ; Hu, Fang ; Zhao, Hailu</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c386t-7b3ec11cd3672e7266efaa982fcc7437e1a888ef4a35d99410f057dfb5df7e343</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2016</creationdate><topic>Angiotensin I converting enzyme 2</topic><topic>Asian Continental Ancestry Group - genetics</topic><topic>Carriers</topic><topic>China</topic><topic>Cohort Studies</topic><topic>Diabetes</topic><topic>Diabetes Mellitus, Type 2 - genetics</topic><topic>Diabetic Nephropathies - genetics</topic><topic>Diabetic Nephropathies - pathology</topic><topic>Enzymes</topic><topic>Female</topic><topic>Filtration</topic><topic>Genetic Association Studies</topic><topic>Genotype</topic><topic>Glomerular Filtration Rate - genetics</topic><topic>Humans</topic><topic>Hypertension</topic><topic>Hypertension - complications</topic><topic>Immunophenotyping</topic><topic>Lipids - blood</topic><topic>Male</topic><topic>Middle Aged</topic><topic>Nodular glomerulosclerosis</topic><topic>Nodules</topic><topic>Patients</topic><topic>Polymorphism</topic><topic>Polymorphism, Genetic</topic><topic>Proteinuria - genetics</topic><topic>Renin-angiotensin system</topic><topic>Renin-Angiotensin System - genetics</topic><topic>Renin-Angiotensin System - immunology</topic><topic>Retrospective Studies</topic><topic>Type 2 diabetes</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Wang, Min</creatorcontrib><creatorcontrib>Zhang, Xiaoxi</creatorcontrib><creatorcontrib>Song, Xinnan</creatorcontrib><creatorcontrib>Zou, Xia</creatorcontrib><creatorcontrib>Wu, Weijie</creatorcontrib><creatorcontrib>Wang, Yanchao</creatorcontrib><creatorcontrib>Lin, Bingjie</creatorcontrib><creatorcontrib>Li, Rong</creatorcontrib><creatorcontrib>Hu, Fang</creatorcontrib><creatorcontrib>Zhao, Hailu</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Solid State and Superconductivity Abstracts</collection><collection>Technology Research Database</collection><collection>Advanced Technologies Database with Aerospace</collection><jtitle>Molecular and cellular endocrinology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Wang, Min</au><au>Zhang, Xiaoxi</au><au>Song, Xinnan</au><au>Zou, Xia</au><au>Wu, Weijie</au><au>Wang, Yanchao</au><au>Lin, Bingjie</au><au>Li, Rong</au><au>Hu, Fang</au><au>Zhao, Hailu</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Nodular glomerulosclerosis and renin angiotensin system in Chinese patients with type 2 diabetes</atitle><jtitle>Molecular and cellular endocrinology</jtitle><addtitle>Mol Cell Endocrinol</addtitle><date>2016-05-15</date><risdate>2016</risdate><volume>427</volume><spage>92</spage><epage>100</epage><pages>92-100</pages><issn>0303-7207</issn><eissn>1872-8057</eissn><abstract>Diabetic nephropathy (DN) is a multifactorial and polygenic disease with nodular glomerulosclerosis (NGS) pathognomonic for diabetes and hypertension. Patients with type 2 diabetes and hypertension have characteristic renin-angiotensin system (RAS) gene polymorphisms.
In this retrospective cohort study, we correlated the presence of NGS with renal function, angiotensin-converting enzyme (ACE) genotypes (DD, DI, and II), angiotensinogen (AGT) genotypes (MM, MT, and TT) and immunohistochemical staining characteristics of RAS components in 847 patients and 172 consecutive autopsy cases with type 2 diabetes. T allele of AGT was associated with macroalbuminuria (P = 0.040). Multitude regression analysis revealed ACE insertion (I)/deletion (D) polymorphism as an independent determinant for estimated glomerular filtration rate (eGFR) less than 60 mL min−1·1.73 m−2 (DD carriers: odds ratio [OR] = 3.46, 95% confidence interval [CI] = 1.08–11.07; DI carriers: OR = 3.51, 95% CI = 1.63–7.56). A significant association between NGS and eGFR less than 60 mL min−1·1.73 m−2 also persisted after adjusting for nonlinear relationship (P < 0.001). In NGS patients, immunoreactivity of angiotensin I converting enzyme 2 (ACE2) significantly decreased in glomeruli with mesangial nodules compared with glomeruli without the mesangial nodules.
These data suggest associations of ACE D allele with glomerular filtration impairment, and NGS with glomerular ACE2 down-regulation and reduced glomerular filtration in Chinese patients with type 2 diabetes.
•This study reveals an association of RAS components and NGS in patients and autopsy cases with type 2 diabetes.•The patients with ACE D or AGT T alleles might have reduced eGFR and macroalbuminuria.•Difference in the immunoreactivity of ACE2 may contribute to the development of nodular glomerulosclerosis.</abstract><cop>Ireland</cop><pub>Elsevier Ireland Ltd</pub><pmid>26973293</pmid><doi>10.1016/j.mce.2016.03.008</doi><tpages>9</tpages></addata></record> |
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| subjects | Angiotensin I converting enzyme 2 Asian Continental Ancestry Group - genetics Carriers China Cohort Studies Diabetes Diabetes Mellitus, Type 2 - genetics Diabetic Nephropathies - genetics Diabetic Nephropathies - pathology Enzymes Female Filtration Genetic Association Studies Genotype Glomerular Filtration Rate - genetics Humans Hypertension Hypertension - complications Immunophenotyping Lipids - blood Male Middle Aged Nodular glomerulosclerosis Nodules Patients Polymorphism Polymorphism, Genetic Proteinuria - genetics Renin-angiotensin system Renin-Angiotensin System - genetics Renin-Angiotensin System - immunology Retrospective Studies Type 2 diabetes |
| title | Nodular glomerulosclerosis and renin angiotensin system in Chinese patients with type 2 diabetes |
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