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Thrombotic risk determined by rare and common SERPINA1 variants in a population-based cohort study

Manderstedt, E. ; Halldén, Christer ; Lind-Halldén, Christina ; Elf, J. LU ; Svensson, P.J. LU ; Engström, G. LU ; Melander, O. LU orcid ; Baras, Aris ; Lotta, Luca A. and Zöller, B. LU orcid (2022) In Journal of Thrombosis and Haemostasis 20(6).
Abstract
Background: Severe alpha-1-antitrypsin deficiency (AATD), phenotype PiZZ, was associated with venous thromboembolism (VTE) in a case-control study. Objectives: This study aimed to determine the genetic variation in the SERPINA1 gene and a possible thrombotic risk of these variants in a population-based cohort study. Patients/Methods: The coding sequence of SERPINA1 was analyzed for the Z (rs28929474), S (rs17580), and other qualifying variants in 28,794 subjects without previous VTE (born 1923–1950, 60% women), who participated in the Malmö Diet and Cancer study (1991–1996). Individuals were followed from baseline until the first event of VTE, death, or 2018. Results: Resequencing the coding sequence of SERPINA1 identified 84 variants in... (More)
Background: Severe alpha-1-antitrypsin deficiency (AATD), phenotype PiZZ, was associated with venous thromboembolism (VTE) in a case-control study. Objectives: This study aimed to determine the genetic variation in the SERPINA1 gene and a possible thrombotic risk of these variants in a population-based cohort study. Patients/Methods: The coding sequence of SERPINA1 was analyzed for the Z (rs28929474), S (rs17580), and other qualifying variants in 28,794 subjects without previous VTE (born 1923–1950, 60% women), who participated in the Malmö Diet and Cancer study (1991–1996). Individuals were followed from baseline until the first event of VTE, death, or 2018. Results: Resequencing the coding sequence of SERPINA1 identified 84 variants in the total study population, 21 synonymous, 62 missense, and 1 loss-of-function variant. Kaplan-Meier analysis showed that homozygosity for the Z allele increased the risk of VTE whereas heterozygosity showed no effect. The S (rs17580) variant was not associated with VTE. Thirty-one rare variants were qualifying and included in collapsing analysis using the following selection criteria, loss of function, in frame deletion or non-benign (PolyPhen-2) missense variants with minor allele frequency (MAF) (Less)
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author
; ; ; ; ; ; ; ; and
author collaboration
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
alpha-1-antitrypsin, epidemiology, genetics, SERPINA1, venous thromboembolism
in
Journal of Thrombosis and Haemostasis
volume
20
issue
6
publisher
Elsevier
external identifiers
  • scopus:85126760431
  • pmid:35263815
ISSN
1538-7933
DOI
10.1111/jth.15696
language
English
LU publication?
yes
id
1ab099e7-90b8-4ca2-8d8e-874c69777266
date added to LUP
2022-09-05 14:23:24
date last changed
2025-10-14 12:26:14
@article{1ab099e7-90b8-4ca2-8d8e-874c69777266,
  abstract     = {{Background: Severe alpha-1-antitrypsin deficiency (AATD), phenotype PiZZ, was associated with venous thromboembolism (VTE) in a case-control study. Objectives: This study aimed to determine the genetic variation in the SERPINA1 gene and a possible thrombotic risk of these variants in a population-based cohort study. Patients/Methods: The coding sequence of SERPINA1 was analyzed for the Z (rs28929474), S (rs17580), and other qualifying variants in 28,794 subjects without previous VTE (born 1923–1950, 60% women), who participated in the Malmö Diet and Cancer study (1991–1996). Individuals were followed from baseline until the first event of VTE, death, or 2018. Results: Resequencing the coding sequence of SERPINA1 identified 84 variants in the total study population, 21 synonymous, 62 missense, and 1 loss-of-function variant. Kaplan-Meier analysis showed that homozygosity for the Z allele increased the risk of VTE whereas heterozygosity showed no effect. The S (rs17580) variant was not associated with VTE. Thirty-one rare variants were qualifying and included in collapsing analysis using the following selection criteria, loss of function, in frame deletion or non-benign (PolyPhen-2) missense variants with minor allele frequency (MAF)}},
  author       = {{Manderstedt, E. and Halldén, Christer and Lind-Halldén, Christina and Elf, J. and Svensson, P.J. and Engström, G. and Melander, O. and Baras, Aris and Lotta, Luca A. and Zöller, B.}},
  issn         = {{1538-7933}},
  keywords     = {{alpha-1-antitrypsin; epidemiology; genetics; SERPINA1; venous thromboembolism}},
  language     = {{eng}},
  number       = {{6}},
  publisher    = {{Elsevier}},
  series       = {{Journal of Thrombosis and Haemostasis}},
  title        = {{Thrombotic risk determined by rare and common SERPINA1 variants in a population-based cohort study}},
  url          = {{http://dx.doi.org/10.1111/jth.15696}},
  doi          = {{10.1111/jth.15696}},
  volume       = {{20}},
  year         = {{2022}},
}