Potential impact of two functional variants in the VEGF gene on the risk and clinical characteristics of granulomatosis with polyangiitis: A case-control study

Abstract

Background: Granulomatosis with polyangiitis (GPA) is an autoimmune disorder that results from an interplay of genetic factors and environmental influences. We investigated the association between two polymorphisms in the VEGF gene, specifically rs2010963 and rs833061, and the likelihood of developing GPA. Methods: A case-control study involving 224 participants was conducted, comprising 104 individuals diagnosed with GPA and 120 control subjects. The high-resolution melting (HRM) technique was employed for genotyping these polymorphisms. Results: The findings revealed a significant difference in the distribution of the CC genotype and C allele for rs2010963 between the control and case groups (CC vs GG; OR: 2.687; 95% CI [1.185-6.264], P: 0.014; C vs G; OR: 1.628; 95% CI [1.097-2.421], P: 0.012). Moreover, patients with the GC + CC genotype exhibited elevated mean levels of creatinine, erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP), as well as a higher incidence of alveolar hemorrhage compared to those with the GG genotype. Concerning rs833061, no association with GPA risk was identified; however, correlations were noted with certain laboratory and clinical parameters, including PR3-ANCA levels, septal perforation, alveolar hemorrhage, renal involvement, and rapidly progressive glomerulonephritis (RPGN). Conclusion: The C allele of rs2010963 is linked to an increased risk of developing GPA and certain laboratory and clinical parameters, while the rs833061 polymorphism does not appear to be associated with GPA risk but is correlated with various laboratory and clinical indices.