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Aldose reductase genotypes and cardiorenal complications: an 8-year prospective analysis of 1,074 type 2 diabetic patients.

So WY, Wang Y, Ng MC, Yang X, Ma RC, Lam V, Kong AP, Tong PC, Chan JC - Diabetes Care (2008)

Bottom Line: In this expanded cohort, we examined their predictive roles on new onset of cardiorenal complications using a prospective design.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.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong SAR, China.

ABSTRACT

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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Cumulative incidence of cardiorenal end point stratified by the number of risk alleles of the z−2 allele of the 5′-(CA)n microsatellite and C-106T promoter polymorphisms of the ALR2 gene (Ptrend 0.002, log-rank test) in type 2 diabetes. +ve, positive; -ve, negative.
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f2: Cumulative incidence of cardiorenal end point stratified by the number of risk alleles of the z−2 allele of the 5′-(CA)n microsatellite and C-106T promoter polymorphisms of the ALR2 gene (Ptrend 0.002, log-rank test) in type 2 diabetes. +ve, positive; -ve, negative.

Mentions: On multivariable analysis, the z−2 allele of −(CA)n and C-106T polymorphisms of ALR2 were selected as independent predictors for renal or cardiorenal end points along with age, male sex, and smoking status. The presence of two risk-conferring genotypes conferred a twofold increased risk of renal or cardiorenal end points (Table 3). Figures 1 and 2 show the cumulative effects of a number of risk-conferring genotypes on renal and cardiorenal end points.


Aldose reductase genotypes and cardiorenal complications: an 8-year prospective analysis of 1,074 type 2 diabetic patients.

So WY, Wang Y, Ng MC, Yang X, Ma RC, Lam V, Kong AP, Tong PC, Chan JC - Diabetes Care (2008)

Cumulative incidence of cardiorenal end point stratified by the number of risk alleles of the z−2 allele of the 5′-(CA)n microsatellite and C-106T promoter polymorphisms of the ALR2 gene (Ptrend 0.002, log-rank test) in type 2 diabetes. +ve, positive; -ve, negative.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2571065&req=5

f2: Cumulative incidence of cardiorenal end point stratified by the number of risk alleles of the z−2 allele of the 5′-(CA)n microsatellite and C-106T promoter polymorphisms of the ALR2 gene (Ptrend 0.002, log-rank test) in type 2 diabetes. +ve, positive; -ve, negative.
Mentions: On multivariable analysis, the z−2 allele of −(CA)n and C-106T polymorphisms of ALR2 were selected as independent predictors for renal or cardiorenal end points along with age, male sex, and smoking status. The presence of two risk-conferring genotypes conferred a twofold increased risk of renal or cardiorenal end points (Table 3). Figures 1 and 2 show the cumulative effects of a number of risk-conferring genotypes on renal and cardiorenal end points.

Bottom Line: In this expanded cohort, we examined their predictive roles on new onset of cardiorenal complications using a prospective design.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.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong SAR, China.

ABSTRACT

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.

Show MeSH
Related in: MedlinePlus