Polymorphisms of the UCP2 gene are associated with proliferative diabetic retinopathy in patients with diabetes mellitus.
OBJECTIVE
Uncoupling protein 2 (UCP2) plays a role in controlling reactive oxygen species (ROS) production by mitochondria. As ROS overproduction is related to diabetic retinopathy (DR), UCP2 gene polymorphisms might be involved in the development of this complication. We investigated whether the -866G/A (rs659366), Ala55Val (rs660339) and 45 bp insertion/deletion (Ins/Del) polymorphisms in the UCP2 gene might be associated with proliferative DR (PDR).


METHODS
In this case-control study, we analysed 501 type 2 diabetic patients (242 patients with PDR and 259 subjects without any degree of DR) and 196 type 1 diabetic patients (85 cases with PDR and 111 without DR). Haplotypes constructed from the combination of the three UCP2 polymorphisms were inferred using a Bayesian statistical method.


RESULTS
In the type 2 diabetic group, multivariate analyses confirmed that the haplotype [A Val Ins] was an independent risk factor for PDR when present in one [adjusted odds ratio (aOR) = 2.12; P = 0.006], at least one (aOR = 2.75; P = 0.00001), or two copies (aOR = 5.30; P = 0.00001), suggesting an additive model of inheritance. Nevertheless, in type 1 diabetic patients, the association of this haplotype with PDR was confirmed only when it was present in at least one (aOR = 2.68; P = 0.014) or two copies (aOR = 6.02; P = 0.005).


CONCLUSIONS
The haplotype [A Val Ins] seems to be an important risk factor associated with PDR in both type 2 and 1 diabetic groups.
Crispim
Daisy
D
Endocrine Division, Hospital de Clínicas de Porto Alegre. daisy_crispim@hotmail.com
Fagundes
Nelson J R
NJ
dos Santos
Kátia G
KG
Rheinheimer
Jakeline
J
Bouças
Ana P
AP
de Souza
Bianca M
BM
Macedo
Gabriel S
GS
Leiria
Leonardo B
LB
Gross
Jorge L
JL
Canani
Luís H
LH
D000368:Aged; D001499:Bayes Theorem; D016022:Case-Control Studies; D003922:Diabetes Mellitus, Type 1 / Q000150:complications*; D003924:Diabetes Mellitus, Type 2 / Q000150:complications*; D003930:Diabetic Retinopathy / Q000150:complications / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D054643:INDEL Mutation; D007473:Ion Channels / Q000235:genetics*; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D024101:Mitochondrial Proteins / Q000235:genetics*; D016017:Odds Ratio; D011110:Polymorphism, Genetic; D000071246:Uncoupling Protein 2
D007473:Ion Channels; D024101:Mitochondrial Proteins; C000604389:UCP2 protein, human; D000071246:Uncoupling Protein 2