Genetic Examination of SETD7 and SUV39H1/H2 Methyltransferases and the Risk of Diabetes Complications in Patients With Type 1 Diabetes
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 markers 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.
RESEARCH DESIGN AND METHODS In the Finnish Diabetic Nephropathy Study (FinnDiane) cohort, 37 tagSNPs were genotyped in 2,991 individuals with type 1 diabetes and diabetic retinopathy, diabetic nephropathy, and cardiovascular disease. Seven single nucleotide polymorphisms (SNPs) were genotyped in the replication cohorts from the Steno Diabetes Center and All Ireland/Warren 3/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.
- Received January 21, 2011.
- Accepted July 11, 2011.
- © 2011 by the American Diabetes Association.
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