The following is a summary of “Association of Genetic Variants of HLA-DQA1 with Bullous Pemphigoid Induced by Dipeptidyl Peptidase-4 Inhibitors,” published in the November 2023  issue of Dermatology by Ozeki et al.

It is the most frequent kind of autoimmune blistering illness, and its name is bullous pemphigoid (BP). BP has been documented to be triggered by several different reasons, one of which is an anti-diabetic medication known as a dipeptidyl peptidase-4 inhibitor (DPP-4i). GWAS and HLA fine-mapping investigations were carried out to determine the genetic variations linked to high blood pressure. In the first cohort, 21 instances of noninflammatory blood pressure (BP) were caused by DPP-4i (also known as DPP-4i-induced noninflammatory blood pressure), and there were 737 controls. 

However, the second cohort had 8 cases and 164 controls. The combination of genome-wide association studies (GWAS) had the effect of satisfying the genome-wide substantial association of HLA-DQA1 (chromosome 6, rs3129763 [T/C]) with the risk of DPP-4i-induced noninflammatory blood pressure (allele T carrier of 72.4% [21 of 29] in cases compared to 15.3% [138 of 901] in controls; dominant model, odds ratio = 14, P  = 1.8 x 10^-9) from the study. 

Based on the results of HLA fine mapping, it was shown that HLA-DQA1∗05, which contains serine at position 75 of HLA-DQα1 (Ser75), had the most significant connection with the combined cohort of DPP-4i−induced noninflammatory blood pressure (79.3% [23 of 29] cases compared to 16.1% [145 of 901] controls; the dominant model had an odds ratio of 21, and the sample size was 2.0 × 10^-10). The polymorphism belonging to HLA-DQα1 Ser75 was situated inside the functional pocket of HLA-DQ molecules, indicating the influence of HLA-DQα1 Ser75 on the noninflammatory blood pressure that DPP-4i causes.

Source: Genetic Variants of HLA-DQA1 Associated with Bullous Pemphigoid Induced by Dipeptidyl Peptidase-4 Inhibitors

Source: sciencedirect.com/science/article/abs/pii/S0022202X23020572