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Genetic risk factor for skin reaction to diabetes drug identified

Non-inflammatory bullous pemphigoid (BP) seen in the type 2 diabetes patient who are administered with DPP-4 inhibitor. Photo by: Hokkaido University

The first genetic risk factor for bullous pemphigoid (BP) arising from DPP-4 inhibitor (DPP-4i) treatment of type-2 diabetes has been identified by researchers from Japan.

Published online ahead of print in the Journal of Investigative Dermatology (Dec. 1, 2017), the study included 30 BP patients who had been treated with DPP-4i, and investigated their symptoms and autoantibodies to categorize them as having inflammatory or noninflammatory BP.

Human leukocyte antigen (HLA) genes from the 30 patients were then analyzed to identify their white blood cell type, as HLA genes are involved in the development of immune-related conditions.

Investigators also analyzed the HLA of 72 BP patients who had not been treated with DPP-4i, and the HLA of 61 diabetic patients who were using DPP-4i but had not experienced BP. These results were compared to HLA genes of 873 individuals from the Japanese general population.

The authors found that 70% of the 30 BP patients treated with DPP-4i had noninflammatory BP with less reddening of the skin. Some 86% of the noninflammatory BP patients administered with DPP-4i had an HLA gene identified as “HLA-DQB1*03:01.” The rate of having this HLA gene was much higher in this group than was detected among the general population (18%) and in type-2 diabetic patients administered with DPP-4i who did not experience BP (31%). Meanwhile, 26% of BP patients who had not been administered DPP-ri had the HLA-DQB1*03:01 HLA gene.

The findings show HLA-DQB1*03:01 is not linked to ordinary BP nor type-2 diabetes, but is closely associated with the development of BP among DPP-4i takers, according to a press release. “However, as the probability of patients exposed to DPP-4i to develop BP remains unclear, further research investigating a much larger number of cases is needed,” lead author Dr. Hideyuki Ujiie, associate professor, Department of Dermatology, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Japan, said in the release.

“Our results suggest people with HLA-DQB1*03:01 have a higher risk of developing BP when exposed to DPP-4i than those without the HLA gene. The gene could serve as a biomarker to help estimate the risk of developing BP when patients are administered with DPP-4i. The mechanism that connects the HLA gene and BP needs to be addressed to help prevent the development of the disease,” Dr. Ujiie said.

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