title: Analysis of the association between diabetic nephropathy and polymorphisms in the aldose reductase gene in Type 1 and Type 2 diabetes mellitus.
abstract: 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.
authors.affiliation: Division of Molecular and Genetic Medicine, University of Sheffield, Sheffield, UK.
authors.forename: M
authors.initials: M
authors.lastname: Neamat-Allah
authors.forename: S A
authors.initials: SA
authors.lastname: Feeney
authors.forename: D A
authors.initials: DA
authors.lastname: Savage
authors.forename: A P
authors.initials: AP
authors.lastname: Maxwell
authors.forename: R L
authors.initials: RL
authors.lastname: Hanson
authors.forename: W C
authors.initials: WC
authors.lastname: Knowler
authors.forename: A M
authors.initials: AM
authors.lastname: El Nahas
authors.forename: M E
authors.initials: ME
authors.lastname: Plater
authors.forename: J
authors.initials: J
authors.lastname: Shaw
authors.forename: A J
authors.initials: AJ
authors.lastname: Boulton
authors.forename: G W
authors.initials: GW
authors.lastname: Duff
authors.forename: A
authors.initials: A
authors.lastname: Cox
mesh_terms: 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
chemical_list: D000449:Aldehyde Reductase; D006442:Glycated Hemoglobin