title: Genetic examination of SETD7 and SUV39H1/H2 methyltransferases and the risk of diabetes complications in patients with type 1 diabetes.
abstract: OBJECTIVE
  Hyperglycemia plays a pivotal role in the development and progression of vascular complications, which are the major sources of morbidity and mortality in diabetes. Furthermore, these vascular complications often persist and progress despite improved glucose control, possibly as a result of prior episodes of hyperglycemia. Epigenetic modifications mediated by histone methyltransferases are associated with gene-activating events that promote enhanced expression of key proinflammatory molecules implicated in vascular injury. In this study, we investigated genetic polymorphisms of the SETD7, SUV39H1, and SUV39H2 methyltransferases as predictors of risk for micro- and macrovascular complications in type 1 diabetes.
  
  
  METHODS
  In the Finnish Diabetic Nephropathy Study (FinnDiane) cohort, 37 tagging single nucleotide polymorphisms (SNPs) were genotyped in 2,991 individuals with type 1 diabetes and diabetic retinopathy, diabetic nephropathy, and cardiovascular disease. Seven SNPs were genotyped in the replication cohorts from the Steno Diabetes Center and All Ireland/Warren 3/Genetics of Kidneys in Diabetes (GoKinD) U.K. study.
  
  
  RESULTS
  In a meta-analysis, the minor T allele of the exonic SNP rs17353856 in the SUV39H2 was associated with diabetic retinopathy (genotypic odds ratio 0.75, P = 1.2 × 10(-4)). The same SNP showed a trend toward an association with diabetic nephropathy as well as cardiovascular disease in the FinnDiane cohort.
  
  
  CONCLUSIONS
  Our findings propose that a genetic variation in a gene coding for a histone methyltransferase is protective for a diabetic microvascular complication. The pathophysiological implications of this polymorphism or other genetic variation nearby for the vascular complications of type 1 diabetes remain to be investigated.
authors: Folkhälsan Institute of Genetics, Folkhälsan Research Center, Biomedicum Helsinki, Helsinki, Finland.
authors: Anna
authors: A
authors: Syreeni
authors: Assam
authors: A
authors: El-Osta
authors: Carol
authors: C
authors: Forsblom
authors: Niina
authors: N
authors: Sandholm
authors: Maikki
authors: M
authors: Parkkonen
authors: Lise
authors: L
authors: Tarnow
authors: Hans-Henrik
authors: HH
authors: Parving
authors: Amy J
authors: AJ
authors: McKnight
authors: Alexander P
authors: AP
authors: Maxwell
authors: Mark E
authors: ME
authors: Cooper
authors: Per-Henrik
authors: PH
authors: Groop
mesh_terms: D000328:Adult; D002318:Cardiovascular Diseases / Q000235:genetics; D015331:Cohort Studies; D003922:Diabetes Mellitus, Type 1 / Q000150:complications* / Q000235:genetics; D003925:Diabetic Angiopathies / Q000235:genetics* / Q000473:pathology; D003928:Diabetic Nephropathies / Q000235:genetics*; D003930:Diabetic Retinopathy / Q000235:genetics*; D005091:Exons; D005260:Female; D005387:Finland; D005787:Gene Frequency; D056726:Genetic Association Studies; D011495:Histone-Lysine N-Methyltransferase / Q000235:genetics*; D006801:Humans; D008297:Male; D008780:Methyltransferases / Q000235:genetics*; D055806:Microvessels / Q000473:pathology; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012097:Repressor Proteins / Q000235:genetics*
chemical_list: D012097:Repressor Proteins; C407843:SUV39H1 protein, human; D008780:Methyltransferases; D011495:Histone-Lysine N-Methyltransferase; C540312:SETD7 protein, human; C515701:SUV39H2 protein, human