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Aldose Reductase Genotypes and Cardiorenal Complications: An 8-year prospective analysis of 1,074 type 2 diabetic patients

OBJECTIVE—We report the independent risk association of type 2 diabetic nephropathy with the z−2 allele of the 5′-(CA)(n) microsatellite and C-106T promoter polymorphisms of the aldose reductase gene (ALR2) using a case-control design. In this expanded cohort, we examined their predictive roles on n...

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Autores principales: So, Wing-Yee, Wang, Ying, Ng, Maggie C.Y., Yang, Xilin, Ma, Ronald C.W., Lam, Vincent, Kong, Alice P.S., Tong, Peter C.Y., Chan, Juliana C.N.
Formato: Texto
Lenguaje:English
Publicado: American Diabetes Association 2008
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2571065/
https://www.ncbi.nlm.nih.gov/pubmed/18716049
http://dx.doi.org/10.2337/dc08-0712
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author So, Wing-Yee
Wang, Ying
Ng, Maggie C.Y.
Yang, Xilin
Ma, Ronald C.W.
Lam, Vincent
Kong, Alice P.S.
Tong, Peter C.Y.
Chan, Juliana C.N.
author_facet So, Wing-Yee
Wang, Ying
Ng, Maggie C.Y.
Yang, Xilin
Ma, Ronald C.W.
Lam, Vincent
Kong, Alice P.S.
Tong, Peter C.Y.
Chan, Juliana C.N.
author_sort So, Wing-Yee
collection PubMed
description OBJECTIVE—We report the independent risk association of type 2 diabetic nephropathy with the z−2 allele of the 5′-(CA)(n) microsatellite and C-106T promoter polymorphisms of the aldose reductase gene (ALR2) using a case-control design. In this expanded cohort, we examined their predictive roles on new onset of cardiorenal complications using a prospective design. RESEARCH DESIGN AND METHODS—In this 8-year prospective cohort of 1,074 type 2 diabetic patients (59% male, median age 61 years; disease duration 7 years) with an observation period of 8,592 person-years, none had clinical evidence of coronary heart disease (CHD) or chronic kidney disease at recruitment. The renal end point was defined as new onset of estimated glomerular filtration rate <60 ml/min per 1.72 m(2) or hospitalizations with dialysis or death due to renal disease, and CHD was defined as hospitalizations with myocardial infarction, ischemic heart disease, or related deaths. RESULTS—After controlling for baseline risk factors and use of medications, we found that the ALR2 z−2 allele of (CA)(n) microsatellite carriers had increased risk of renal (hazard ratio 1.53 [95% CI 1.14–2.05], P = 0.005) or combined cardiorenal (1.31 [1.01–1.72], P = 0.047) end points. Carriers of the ALR2 C-106T polymorphism also had increased risk of renal (1.54 [1.15–2.07], P = 0.004) and cardiorenal (1.49 [1.14–1.95], P = 0.004) end points. Compared with noncarriers, patients with two risk-conferring genotypes had a twofold increased risk of renal (2.41 [1.57–3.70], P < 0.001) and cardiorenal (1.94 [1.29–2.91], P = 0.002) end points. CONCLUSIONS—In Chinese type 2 diabetic patients, genetic polymorphisms of ALR2 independently predicted new onset of renal and cardiorenal end points, with the latter being largely mediated through renal disease.
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spelling pubmed-25710652009-11-01 Aldose Reductase Genotypes and Cardiorenal Complications: An 8-year prospective analysis of 1,074 type 2 diabetic patients So, Wing-Yee Wang, Ying Ng, Maggie C.Y. Yang, Xilin Ma, Ronald C.W. Lam, Vincent Kong, Alice P.S. Tong, Peter C.Y. Chan, Juliana C.N. Diabetes Care Epidemiology/Health Services Research OBJECTIVE—We report the independent risk association of type 2 diabetic nephropathy with the z−2 allele of the 5′-(CA)(n) microsatellite and C-106T promoter polymorphisms of the aldose reductase gene (ALR2) using a case-control design. In this expanded cohort, we examined their predictive roles on new onset of cardiorenal complications using a prospective design. RESEARCH DESIGN AND METHODS—In this 8-year prospective cohort of 1,074 type 2 diabetic patients (59% male, median age 61 years; disease duration 7 years) with an observation period of 8,592 person-years, none had clinical evidence of coronary heart disease (CHD) or chronic kidney disease at recruitment. The renal end point was defined as new onset of estimated glomerular filtration rate <60 ml/min per 1.72 m(2) or hospitalizations with dialysis or death due to renal disease, and CHD was defined as hospitalizations with myocardial infarction, ischemic heart disease, or related deaths. RESULTS—After controlling for baseline risk factors and use of medications, we found that the ALR2 z−2 allele of (CA)(n) microsatellite carriers had increased risk of renal (hazard ratio 1.53 [95% CI 1.14–2.05], P = 0.005) or combined cardiorenal (1.31 [1.01–1.72], P = 0.047) end points. Carriers of the ALR2 C-106T polymorphism also had increased risk of renal (1.54 [1.15–2.07], P = 0.004) and cardiorenal (1.49 [1.14–1.95], P = 0.004) end points. Compared with noncarriers, patients with two risk-conferring genotypes had a twofold increased risk of renal (2.41 [1.57–3.70], P < 0.001) and cardiorenal (1.94 [1.29–2.91], P = 0.002) end points. CONCLUSIONS—In Chinese type 2 diabetic patients, genetic polymorphisms of ALR2 independently predicted new onset of renal and cardiorenal end points, with the latter being largely mediated through renal disease. American Diabetes Association 2008-11 /pmc/articles/PMC2571065/ /pubmed/18716049 http://dx.doi.org/10.2337/dc08-0712 Text en Copyright © 2008, American Diabetes Association https://creativecommons.org/licenses/by-nc-nd/3.0/Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. See http://creativecommons.org/licenses/by-nc-nd/3.0/ for details.
spellingShingle Epidemiology/Health Services Research
So, Wing-Yee
Wang, Ying
Ng, Maggie C.Y.
Yang, Xilin
Ma, Ronald C.W.
Lam, Vincent
Kong, Alice P.S.
Tong, Peter C.Y.
Chan, Juliana C.N.
Aldose Reductase Genotypes and Cardiorenal Complications: An 8-year prospective analysis of 1,074 type 2 diabetic patients
title Aldose Reductase Genotypes and Cardiorenal Complications: An 8-year prospective analysis of 1,074 type 2 diabetic patients
title_full Aldose Reductase Genotypes and Cardiorenal Complications: An 8-year prospective analysis of 1,074 type 2 diabetic patients
title_fullStr Aldose Reductase Genotypes and Cardiorenal Complications: An 8-year prospective analysis of 1,074 type 2 diabetic patients
title_full_unstemmed Aldose Reductase Genotypes and Cardiorenal Complications: An 8-year prospective analysis of 1,074 type 2 diabetic patients
title_short Aldose Reductase Genotypes and Cardiorenal Complications: An 8-year prospective analysis of 1,074 type 2 diabetic patients
title_sort aldose reductase genotypes and cardiorenal complications: an 8-year prospective analysis of 1,074 type 2 diabetic patients
topic Epidemiology/Health Services Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2571065/
https://www.ncbi.nlm.nih.gov/pubmed/18716049
http://dx.doi.org/10.2337/dc08-0712
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