Analysis of the association between diabetic nephropathy and polymorphisms in the aldose reductase gene in Type 1 and Type 2 diabetes mellitus.
OBJECTIVE
To investigate the association between polymorphisms of the aldose reductase gene and diabetic nephropathy in both Type 1 and Type 2 diabetes mellitus, and to carry out a meta-analysis of published results.


METHODS
We have investigated the role of two aldose reductase polymorphisms in four independent cohorts of cases and controls (two each with Type 1 and Type 2 diabetes) drawn from two ethnic populations, including 471 patients with nephropathy and 494 control diabetic patients without nephropathy. A C/T transition at position -106, and a (CA)n microsatellite marker 2.1 kb from the start site of the aldose reductase gene were genotyped in nephropathic patients and non-nephropathic controls from each cohort.


RESULTS
Carriage of the -106 T allele was significantly associated with diabetic nephropathy in three of the four study groups. The Mantel-Haenszel combined odds ratio was 2.22 (95% CI 1.69, 2.94), P = 1.05 x 10(-8). We found no evidence for association of the microsatellite marker with nephropathy, despite moderate levels of disequilibrium between the two markers. Meta-analysis of published data yielded no evidence for association of the microsatellite marker with diabetic nephropathy in Type 2 diabetes, but varying degrees of association with diabetic nephropathy in Type 1 diabetes.


CONCLUSIONS
Meta-analyses provide more convincing evidence of a role for the ALR2-106 marker than for the microsatellite marker in diabetic nephropathy (DN). More studies are now required to confirm these results and to establish whether the ALR2-106 polymorphism has a functional role in DN.
Neamat-Allah
M
M
Division of Molecular and Genetic Medicine, University of Sheffield, Sheffield, UK.
Feeney
S A
SA
Savage
D A
DA
Maxwell
A P
AP
Hanson
R L
RL
Knowler
W C
WC
El Nahas
A M
AM
Plater
M E
ME
Shaw
J
J
Boulton
A J
AJ
Duff
G W
GW
Cox
A
A
D000293:Adolescent; D000328:Adult; D000368:Aged; D000449:Aldehyde Reductase / Q000235:genetics*; D000483:Alleles; D002648:Child; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics*; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics*; D003928:Diabetic Nephropathies / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006442:Glycated Hemoglobin / Q000032:analysis; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D018895:Microsatellite Repeats; D008875:Middle Aged; D016017:Odds Ratio; D011110:Polymorphism, Genetic
D000449:Aldehyde Reductase; D006442:Glycated Hemoglobin