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Study of genetic variants of the GLP1R gene in bullous pemphigoid” (Bachelor thesis)

Ρότα, Ναταλία/ Rota, Natalia

Bullous pemphigoid is the most prevalent autoimmune skin disease, predominantly affecting individuals aged 65 years and older. It is characterized by subepidermal blistering on the body trunk and limbs, which result from the detachment of the epidermis from the underlying layer, the dermis. The mechanism of development of bullous pemphigoid involves the deposition of autoantibodies against the BP180 and BP230 antigens of the hemidesmosomes leading to complement activation, which contributes to blister formation. Genetic predisposition plays a major role in the appearance of the disease, with many genes already associated with the idiopathic form as well as the drug-induced form. This study focuses on the GLP-1R gene, which encodes a receptor involved in the insulin secretion pathway from beta-pancreatic cells, while also being expressed in other tissues contributing to neuroprotection, normal heart function and glomerular filtration in the kidneys, highlighting the important role of this receptor. Antidiabetic drugs such as gliptins have already been associated with the disease and contribute to the activation of the receptor being studied. The aim of this study was to investigate the rs6923761 polymorphism of the GLP-1R gene, in order to identify an association with bullous pemphigoid. This study included patients with the idiopathic form of the disease, patients with type 2 diabetes mellitus and drug-induced bullous pemphigoid, patients with type 2 diabetes mellitus receiving gliptin treatment who did not develop bullous pemphigoid and individuals with no history of bullous pemphigoid. In order to establish associations of the polymorphism with the disease, genotyping of the individuals was performed using the RFLP-PCR technique following DNA isolation from blood samples. Our results show a significant statistical association of the GG genotype (wild type) with the drug-induced form of bullous pemphigoid caused by gliptin therapy, whereas the GA and AA genotypes appeared to have a protective effect against the disease. The GG genotype may be associated with gliptin-associated bullous pemphigoid, possibly through mechanisms involving enhanced immune activation in individuals receiving gliptin therapy.