ArticleClinics (Sao Paulo, Brazil)2024
Polymorphisms of the SERPINA1 gene are associated with higher mortality in a Brazilian cohort of ANCA-associated vasculitis patients.
Article in Clinics (Sao Paulo, Brazil), 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
backgroundAlpha-1-Antitrypsin (A1AT) is a protease inhibitor encoded by the SERPINA1 gene. A1AT serves as the primary natural inhibitor of Proteinase 3 (PR3), an enzyme found in neutrophils. PR3 is an antigenic target of Anti-Neutrophil Cytoplasmic Antibodies (ANCA). While numerous studies have established a connection between Single Nucleotide Polymorphisms (SNPs) in the SERPINA1 gene and ANCA-Associated Vasculitis (AAV), limited research has delved into the impact of these polymorphisms on the prognosis of these patients.
objectiveThe present study's objective is to investigate mortality disparities among Brazilian AAV patients carrying SERPINA1 SNPs (rs7151526, rs28929454) compared to non-carriers. Additionally, the authors analyzed demographic, clinical, and serologic data in these two groups.
methodsIn this single-center prospective cohort study, the authors enrolled AAV patients who were monitored for a duration of up to three years. The identification of SNPs was conducted through RT-PCR. Survival analysis, including Kaplan-Meier survival curves, and Cox proportional regression analysis was subsequently performed to evaluate outcomes.
resultsThe authors assessed 115 patients (65.2% with granulomatosis with polyangiitis, 17.4% with eosinophilic granulomatosis with polyangiitis, and 17.4% with microscopic polyangiitis). All patients were aged ≥ 18 years, with 37.4% being female, and 54.7% identified as White. The association between SERPINA1 SNPs proved to be the most significant factor linked to mortality in the cohort (HR = 6.2, 95% CI 1.4‒27.1, p = 0.015). SERPINA1 SNP carriers exhibited a lower mean survival [rs7151526: 57.4 (42.7‒72.2) years, p < 0.007; rs28929454: 54.9 (40.9‒68.9) years, p < 0.0001] than non-carriers (68.0 [67.2‒69.0] years).
conclusionSERPINA1 SNPs are associated with increased mortality in Brazilian AAV patients.
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