title: Putative role of polymorphisms in UCP1-3 genes for diabetic nephropathy.
abstract: Increased production of reactive oxygen species (ROS) has been suggested as a cause of diabetic complications. Uncoupling proteins (UCPs) have been ascribed a role in reducing the formation of ROS, and genetic variation in genes encoding for UCPs could thus be putative candidate genes for diabetic nephropathy. To test this hypothesis we searched for association between the A-->G (-3862) variant in UCP1, the insertion/deletion (I/D) polymorphism in exon 8 in UCP2, and the C-->T (-55) polymorphism in UCP3 and diabetic nephropathy in 218 diabetic patients with normal urinary albumin excretion rate (AER), 216 with micro- or macroalbuminuria, and in 106 control subjects without a family history of diabetes. We did not find any association between the different polymorphisms and diabetic nephropathy, nor did we observe any difference in AER among carriers of different UCP1-3 genotypes. We could, however, confirm the reported association between BMI and the UCP3 -55 C-->T polymorphism; patients carrying the T allele had higher BMI than patients homozygous for the C allele (26.4+/-4.2 vs. 25.3+/-4.3 kg/m(2); P=.01). We conclude that studied polymorphisms in the UCP1-3 genes do not play a major role in the development of micro- or macroalbuminuria in Scandinavian diabetic patients.
authors.affiliation: Department of Endocrinology, University Hospital MAS, SE-205 02 Malmo, Sweden.
authors.forename: Eero
authors.initials: E
authors.lastname: Lindholm
authors.forename: Mia
authors.initials: M
authors.lastname: Klannemark
authors.forename: Elisabet
authors.initials: E
authors.lastname: Agardh
authors.forename: Leif
authors.initials: L
authors.lastname: Groop
authors.forename: Carl-David
authors.initials: CD
authors.lastname: Agardh
mesh_terms: D000419:Albuminuria / Q000235:genetics; D002352:Carrier Proteins / Q000235:genetics*; D017931:DNA Primers; D003928:Diabetic Nephropathies / Q000235:genetics*; D006801:Humans; D007473:Ion Channels; D008565:Membrane Proteins / Q000235:genetics*; D026901:Membrane Transport Proteins / Q000235:genetics*; D024101:Mitochondrial Proteins / Q000235:genetics*; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D017382:Reactive Oxygen Species / Q000037:antagonists & inhibitors; D012537:Scandinavian and Nordic Countries; D000071256:Uncoupling Protein 1; D000071246:Uncoupling Protein 2; D000071247:Uncoupling Protein 3
chemical_list: D002352:Carrier Proteins; D017931:DNA Primers; D007473:Ion Channels; D008565:Membrane Proteins; D026901:Membrane Transport Proteins; D024101:Mitochondrial Proteins; D017382:Reactive Oxygen Species; C000604371:UCP1 protein, human; C000604389:UCP2 protein, human; C000604392:UCP3 protein, human; D000071256:Uncoupling Protein 1; D000071246:Uncoupling Protein 2; D000071247:Uncoupling Protein 3