Association of DPP4 Gene Variants with Classic and DPP4 Inhibitor-Associated Bullous Pemphigoid

Bullous pemphigoid (BP), the most prevalent autoimmune blistering skin disorder, has been associated with dipeptidyl peptidase-4 inhibitor (DPP4i) treatment in type 2 diabetic patients. This study aimed to investigate the association of DPP4 gene variants, rs3788979 and rs12617656, with classic BP (cBP)- and DPP4i-associated BP predisposition. Fifty-six (56) unrelated patients with cBP, 32 DPP4i-associated BP patients, 60 healthy controls, and 49 diabetic patients receiving DPP4i were included. Genotyping was performed using polymerase chain reaction-restriction fragment length polymorphism assay (PCR-RFLP). Statistical analyses were conducted using SPSS software. For rs3788979, the CT+TT genotypes were significantly associated with increased risk of DPP4i-associated BP compared with cBP [(Odds Ratio (OR) = 2.80, 95% Confidence Interval (CI) = 1.07–7.35; p-value = 0.034] and healthy controls (OR = 0.30, 95% CI = 0.13–0.86; p-value = 0.020). The T allele was also enriched in DPP4i-associated BP (OR = 2.57, 95% CI = 1.09–6.07; p-value = 0.027). Additionally, the TC genotype of rs12617656 (OR = 2.29, 95% CI = 1.04–5.03, p-value = 0.039) showed significant association with cBP susceptibility. These findings highlight DPP4 variants as potential BP risk factors, supporting personalized risk assessment prior to initiating gliptin therapy. Large-scale studies are warranted to validate these associations.