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The association of CTLA-4 and CD28 gene polymorphisms with idiopathic ischemic stroke in the paediatric population
1Department of Neurology, Beijing Children's Hospital, The Capital Medical University, Beijing, China.
Insights
Genetic variations in CTLA-4 and CD28 genes are linked to idiopathic childhood ischemic stroke. Specific polymorphisms in CTLA-4 and CD28 may increase the risk of this condition in children.
Area of Science:
- Genetics
- Immunology
- Pediatric Neurology
Background:
- Autoimmune vasculitis is a suspected cause of idiopathic childhood ischemic stroke.
- Polymorphisms in CTLA-4 and CD28 genes are associated with immune vasculitides like SLE and Behçet's disease.
Purpose of the Study:
- To investigate the association between genetic variants in CTLA-4 and CD28 genes and idiopathic childhood ischemic stroke.
- To analyze the risk conferred by specific single nucleotide polymorphisms (SNPs) in these genes.
Main Methods:
- A case-control study design was employed.
- Genotyping of two SNPs in the CTLA-4 gene and one SNP in the CD28 gene was performed.
- 51 patients with idiopathic ischemic stroke and 74 healthy controls from mainland China were included.
Main Results:
- The CTLA-4+49A/G SNP showed a nominal association with the disease (P = 0.012).
- Homozygous carriers of the G allele of CTLA-4+49A/G were more prevalent in patients (P = 0.008).
- The CD28IVS3 +17TT genotype was more common in patients (P = 0.039).
Conclusions:
- Polymorphisms in CTLA-4 and CD28 genes may contribute to the risk of idiopathic childhood ischemic stroke.
- No correlation was found between specific genotypes and clinical features of the stroke.
Abstract:
Autoimmune vasculitis is believed to be a critical factor in the development of idiopathic childhood ischemic stroke. The association of polymorphisms in CTLA-4 and CD28 with some immune vasculitides, such as systemic lupus erythematosus (SLE) and Behçet's disease has been reported. The aim of the present study is to investigate the association of the genetic variants in the CTLA-4 and CD28 genes of children who suffered idiopathic ischemic stroke using a case-control design. Two single nucleotide polymorphisms (SNPs) in the CTLA-4 gene and an SNP in the CD28 gene were genotyped in 51 patients who suffered idiopathic ischemic stroke, and in 74 healthy controls from mainland China. An SNP, CTLA-4+49A/G located in exon 1 of the CTLA-4 gene, showed nominal association with the disease (P = 0.012, odds ratio (OR) = 2.09, 95% confidence interval (CI) = 1.17-3.73) using allele-based analysis. Homozygous carriers of the G allele of this SNP were more common in the patients than in the controls (P = 0.008). The CD28IVS3 +17TT genotype was found to be more common in the patients than in the controls (P = 0.039, OR = 2.96, 95% CI = 1.02-8.58). No correlations of at-risk genotype (G/G) of CTLA-4+49A/G and genotype (T/T) of CD28+17T/C with the main clinical features of idiopathic childhood ischemic stroke were observed. The results suggest that polymorphisms in the CTLA-4 and CD28 genes may contribute to the increased risk of idiopathic ischemic stroke.
