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SAMHD1 Gene Mutations Are Associated with Cerebral Large-Artery Atherosclerosis.
- Source :
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BioMed research international [Biomed Res Int] 2015; Vol. 2015, pp. 739586. Date of Electronic Publication: 2015 Oct 04. - Publication Year :
- 2015
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Abstract
- Background: To investigate whether one or more SAMHD1 gene mutations are associated with cerebrovascular disease in the general population using a Chinese stroke cohort.<br />Methods: 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.<br />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). The mutant SAMHD1 proteins were functionally impaired in terms of their catalytic activity as a dNTPase and ability to assemble stable tetramers.<br />Conclusions: Heterozygous SAMHD1 gene mutations might cause genetic predispositions that interact with other risk factors, resulting in increased vulnerability to stroke.
- Subjects :
- Aged
Asian People genetics
Atherosclerosis epidemiology
Cerebral Arteries diagnostic imaging
China epidemiology
Cohort Studies
DNA Mutational Analysis
Female
Genetic Predisposition to Disease epidemiology
Humans
Male
Middle Aged
Mutation genetics
Radiography
SAM Domain and HD Domain-Containing Protein 1
Stroke epidemiology
Atherosclerosis genetics
Genetic Predisposition to Disease genetics
Monomeric GTP-Binding Proteins genetics
Stroke genetics
Subjects
Details
- Language :
- English
- ISSN :
- 2314-6141
- Volume :
- 2015
- Database :
- MEDLINE
- Journal :
- BioMed research international
- Publication Type :
- Academic Journal
- Accession number :
- 26504826
- Full Text :
- https://doi.org/10.1155/2015/739586