Back to Search
Start Over
Functional SNP in an Sp1-binding site of AGTRL1 gene is associated with susceptibility to brain infarction.
- Source :
-
Human molecular genetics [Hum Mol Genet] 2007 Mar 15; Vol. 16 (6), pp. 630-9. Date of Electronic Publication: 2007 Feb 19. - Publication Year :
- 2007
-
Abstract
- Brain infarction is one of the common causes of death and also a major cause of severe disability. To identify a gene(s) susceptible to brain infarction, we performed a large-scale association study of Japanese patients with brain infarction, using 52608 gene-based single nucleotide polymorphism (SNP) markers. Comparison of allele frequencies between 1112 cases with brain infarction and age- and sex-matched control subjects of the same number found an SNP in the 5'-flanking region of angiotensin receptor like-1 (AGTRL1) gene (rs9943582, - 154G/A) to have a significant association with brain infarction [odds ratio = 1.30, 95% confidence interval (CI) = 1.14-1.47, P = 0.000066]. We also found the binding of Sp1 transcription factor to the region including the susceptible G allele, but not the non-susceptible A allele. Luciferase assay and RT-PCR analysis demonstrated that exogenously introduced Sp1 induced transcription of AGTRL1 and its ligand, apelin, as well, indicating direct regulation of apelin/APJ pathway by Sp1. Furthermore, a 14 year follow-up cohort study in a Japanese community in Hisayama town, Japan revealed that the homozygote of the susceptible G allele of this particular SNP had significantly higher risk of brain infarction (hazard ratio = 2.00, 95% CI = 1.22-3.29, P = 0.006). Our results indicate that the SNP in the AGTRL1 gene is associated with the susceptibility to brain infarction.
- Subjects :
- 5' Flanking Region
Adult
Aged
Aged, 80 and over
Alleles
Apelin
Apelin Receptors
Asian People
Case-Control Studies
Cell Line
Cell Line, Tumor
Cohort Studies
Female
Follow-Up Studies
Gene Expression
Homozygote
Humans
Intercellular Signaling Peptides and Proteins genetics
Japan
Male
Middle Aged
Protein Binding
RNA, Messenger
Risk Factors
Sp1 Transcription Factor metabolism
Brain Infarction genetics
Genetic Predisposition to Disease
Polymorphism, Single Nucleotide
Receptors, G-Protein-Coupled genetics
Receptors, G-Protein-Coupled metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 0964-6906
- Volume :
- 16
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- Human molecular genetics
- Publication Type :
- Academic Journal
- Accession number :
- 17309882
- Full Text :
- https://doi.org/10.1093/hmg/ddm005