Single nucleotide polymorphisms (SNPs) in the gene that encodes one of the thiamine transporters are associated with the risk of patients with type 1 diabetes mellitus (T1DM) developing diabetic retinopathy, according to new research.

Credit: Bram Janssens/iStock/Thinkstock

“Although glycaemic control is the most important risk factor for microvascular complications, some individuals with poor metabolic control do not develop them, whereas others get severe retinopathy and nephropathy despite good glycaemic control, suggesting that genetically determined factors may contribute,” explain authors Massimo Porta and Iiro Toppila. As thiamine is known to be involved in regulating intracellular glucose metabolism, Porta, Toppila and co-workers tested whether 134 SNPs in SLC19A2 and SLC19A3 (which encode thiamine transporters) and SP1 and SP2 (which encode transcription factors for SLC19A2 and SLC19A3) were associated with retinopathy, nephropathy or a combined phenotype of both microvascular complications.

Two SNPs... in SLC19A3 were found to be associated with a reduced risk of severe diabetic retinopathy

The study included 1,566 participants in the FinnDiane Study who had severe diabetic retinopathy, as well as 218 control individuals who either had no diabetic retinopathy or mild disease. Two SNPs (rs12694743 and rs6713116) in SLC19A3 were found to be associated with a reduced risk of severe diabetic retinopathy, as well as with a reduced risk of the combined phenotype of severe diabetic retinopathy and end-stage renal disease. Furthermore, the association between rs12694743 and the combined phenotype reached genome-wide significance when the researchers performed a meta-analysis that included patients from the Wisconsin Epidemiologic Study of Diabetic Retinopathy cohort.

“These findings suggest that genetic variations in SLC19A3 might be involved in the pathogenesis of severe diabetic retinopathy and nephropathy and might help explain why some patients with T1DM are less prone than others to developing microvascular complications,” say Porta and Toppila. The researchers acknowledge that work still needs to be done to determine the mechanisms underlying this association. “In addition, it should be investigated whether genetic testing is useful for identifying which patients with T1DM are less at risk of developing severe complications,” conclude Porta and Toppila.