Thrombotic risk determined by rare and common SERPINA1 variants in a population-based cohort study
(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)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/1ab099e7-90b8-4ca2-8d8e-874c69777266
- author
- Manderstedt, E. ; Halldén, Christer ; Lind-Halldén, Christina ; Elf, J. LU ; Svensson, P.J. LU ; Engström, G. LU ; Melander, O. LU ; Baras, Aris ; Lotta, Luca A. and Zöller, B. LU
- author collaboration
- organization
-
- Clinical Coagulation, Malmö (research group)
- EpiHealth: Epidemiology for Health
- Cardiovascular Research - Epidemiology (research group)
- Cardiovascular Research - Hypertension (research group)
- EXODIAB: Excellence of Diabetes Research in Sweden
- MultiPark: Multidisciplinary research focused on Parkinson´s disease
- Family medicine, cardiovascular medicine and genetics (research group)
- publishing date
- 2022
- 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
- Wiley-Blackwell
- 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
- 2024-01-18 15:36:18
@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 = {{Wiley-Blackwell}}, 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}}, }