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. 2024 Oct 29:79:100524.
doi: 10.1016/j.clinsp.2024.100524. eCollection 2024.

Polymorphisms of the SERPINA1 gene are associated with higher mortality in a Brazilian cohort of ANCA-associated vasculitis patients

Henrique Ayres Mayrink Giardini  1 , Valeria de Falco Caparbo  2 , Isac de Castro  2 , Andréia Padilha Toledo  3 , Carmen Silvia Valente Barbas  3 , Samuel Katsuyuki Shinjo  2 , Rosa Maria Rodrigues Pereira  2
Affiliations

Polymorphisms of the SERPINA1 gene are associated with higher mortality in a Brazilian cohort of ANCA-associated vasculitis patients

Henrique Ayres Mayrink Giardini et al. Clinics (Sao Paulo). .

Abstract

Background: Alpha-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.

Objective: The 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.

Methods: In 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.

Results: The 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).

Conclusion: SERPINA1 SNPs are associated with increased mortality in Brazilian AAV patients.

Keywords: Gene; Mortality; Polymorphism; Systemic vasculitis.

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Conflict of interest statement

Declaration of competing interest The authors declare no conflicts of interest.

Figures

Fig 1
Fig. 1
Cox proportional hazard model: genetic factor and comorbidities. HR, Hazard Ratio; CI, Confidence Interval. The analysis of the association of the SNPs of the SERPINA1 gene was performed due to the linkage disequilibrium between them (association coefficient 0.88, p < 0.001). Statistically significant: p-value < 0.05.
See this image and copyright information in PMC

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