Common coding variant in SERPINA1 increases the risk for large artery stroke

• DOI: 10.1073/pnas.1616301114
• Publication Date: 2017-03-07T02:00:34Z
• Authors: Rainer Malik; Therese Dau; Maria Gonik; Anirudh Sivakumar; Daniel J. Deredge; Evgeniia V. Edeleva; Jessica Götzfried; Sander W. van der...; Gerard Pasterkamp; Nathalie Beaufort; Susana Seixas; Steve Bevan; Lisa F. Lincz; Elizabeth G. Holl...; Annette I. Burgess; Kristiina Rannikmäe; Jens Minnerup; Jennifer Kriebel; Melanie Waldenberger; Martina Müller-Nu...; Peter Lichtner; Danish Saleheen; ; Peter M. Rothwell; Christopher Levi; John Attia; Cathie L. M. Sudlow; Dieter Braun; Hugh S. Markus; Patrick L. Wintrode; Klaus Berger; Dieter E. Jenne; Martin Dichgans; Daniel Woo; Stephanie Debette; Jane Maguire; John W. Cole; Jennifer Majersik; Steve Bevan; Jordi Jimenez-Conde; Jin-Moo Lee; Natalia Rost; Guillaume Pare; Christina Jern; Arne G Lindgren; Israel Fernandez ...
• Keywords: Serpin; Coding region

Significance Common single-amino acid variations of proteins are traditionally regarded as functionally neutral polymorphisms because these substitutions mostly located outside relevant surfaces. In this study, we present an example a coding sequence variation, which, show here, confers risk for large artery atherosclerotic stroke. The single-residue variation M1(A213V) in serpin family A member 1 ( SERPINA1 ) [encoding alpha-1 antitrypsin (AAT)] is situated the protease-reactive inhibitory loop and found β-turn on protein surface. We that Ala-to-Val exchange gate region AAT alters its functional dynamics toward neutrophil elastase presence complex lipid-containing plasma also affects overall structural flexibility protein.