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 new onset of cardiorenal complications using a prospective design.


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.
So
Wing-Yee
WY
Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong SAR, China.
Wang
Ying
Y
Ng
Maggie C Y
MC
Yang
Xilin
X
Ma
Ronald C W
RC
Lam
Vincent
V
Kong
Alice P S
AP
Tong
Peter C Y
PC
Chan
Juliana C N
JC
D000368:Aged; D000449:Aldehyde Reductase / Q000235:genetics*; D000483:Alleles; D044466:Asian People / Q000235:genetics; D003327:Coronary Disease / Q000208:ethnology / Q000209:etiology / Q000235:genetics*; D003924:Diabetes Mellitus, Type 2 / Q000150:complications* / Q000208:ethnology; D003928:Diabetic Nephropathies / Q000208:ethnology / Q000209:etiology / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006723:Hong Kong / Q000453:epidemiology; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D011446:Prospective Studies
D000449:Aldehyde Reductase