Data Management And Sharing System of China National Clinical Research Center for Neurological Diseases
SAMHD1 gene mutations are associated with cerebral large-artery atherosclerosis.
First author：wei li
Corresponding author：yongjun wang,Heng Wang
essential_information
2015-10-04
Published articles
Journal：Biomed Res Int
Publication type: Original Contributions
IF(IF): 3.411
PMID: 26504826 Link To Pubmed Full text Download
Background And Purpose
To investigate whether one or more SAMHD1 gene mutations are associated with cerebrovascular disease in the general population using a Chinese stroke cohort.
Method
Patients with a Chinese Han background (N=300) diagnosed with either cerebral large-artery atherosclerosis (LAA, n=100), cerebral small vessel disease (SVD, n=100), or other stroke-free neurological disorders (control, n=100) were recruited. Genomic DNA from the whole blood of each patient was isolated, and direct sequencing of the SAMHD1 gene was performed. Both wild type and mutant SAMHD1 proteins identified from the patients were expressed in E. coli and purified; then their dNTPase activities and ability to form stable tetramers were analysed in vitro.
Conclusion
Heterozygous SAMHD1 gene mutations might cause genetic predispositions that interact with other risk factors, resulting in increased vulnerability to stroke.
Main results
Three heterozygous mutations, including two missense mutations c.64C>T (P22S) and c.841G>A (p.E281K) and one splice site mutation c.696+2T >A, were identified in the LAA group with a prevalence of 3%. No mutations were found in the patients with SVD or the controls ( p=0.05). he mutant SAMHD1 proteins were functionally impaired in terms of their catalytic activity as a dNTPase and ability to assemble stable tetramers.