Association between two key SNPs on chromosome 12p13 and ischemic stroke in Chinese Han population.
ABSTRACT Genome-wide single nucleotide polymorphism (SNP) association studies recently identified two SNPs (rs11833579 and rs12425791) on chromosome 12p13 that are associated with ischemic stroke (IS) in Caucasian or Black persons from America and the Netherlands. Our aim was to determine whether these SNPs were associated with IS in Chinese Han population.
We used a case-control study involving 648 IS patients and 648 age-matched, sex-matched, and ethnicity-matched non-IS controls from two ethnic populations and determined the genotypes of two polymorphisms by TaqMan SNP genotyping assays to assess any links with IS.
Significant allelic association was identified between rs11833579 and IS in the Han population (odds ratio=1.27, 95% confidence interval=1.08-1.49). One risk haplotype (A-G; odds ratio=1.52, 95% confidence interval=1.21-1.92) was identified in the Han population. Genotypic association analysis demonstrated that rs11833579 confers susceptibility to IS only in a recessive model (P=0.004) rather in additive model. However, the association between rs12425791 and IS was insignificant in Chinese Han population.
The A allele of SNP rs11833579 on chromosome 12p13 may play a role in mediating susceptibility to IS in the Han Chinese population in a recessive model. The A-G haplotype is also significantly associated with higher IS risk in the Han Chinese population. However, larger populations are warranted to validate our findings.
- [Show abstract] [Hide abstract]
ABSTRACT: Meta-analysis in European population found no association between rs12425791/rs11833579 and ischemic stroke. Several studies focused on East Asians have evaluated the association between this two SNPs and risk of ischemic stroke, but the results have been inconsistent. The aim of this study was to perform a meta-analysis to investigate a more authentic association between rs12425791 and rs11833579 G>A mutation and ischemic stroke in East Asian population, as well as in Chinese Han population. Systematic searches of electronic databases Embase, PubMed, Web of Science, and CBM as well as hand searching of the references of identified articles and the meeting abstracts were performed. Study selection, data abstraction and study quality evaluation were independently conducted in duplicate. Statistical analyses were performed using software Stata 11.0. The pooled odds ratios (ORs) with 95% confidence intervals (95%CIs) were performed. Different effects models were used according to the difference in heterogeneity. Publication bias was tested by Begg's funnel plot and Egger's regression test. A total of 4 publications including 7 studies were involved. For rs12425791, significant association was found in allelic model (OR=1.06, 95%CI=1.00-1.11) and dominant model (OR=1.10, 95%CI=1.03-1.18), whereas no evidence of association was found for additive model (OR=1.04, 95%CI=0.93-1.17) and for recessive model (OR=0.99, 95%CI=0.88-1.10). For rs11833579, no evidence of association was found for all genetic models. In the analysis of Chinese Han population, there is lack of evidence for association of ischemic stroke for both SNPs. In summary, our meta-analysis suggests that rs12425791 is significantly associated with ischemic stroke in East Asian population but not Chinese Han population, of which A alleles increase the risk of ischemic stroke, whereas no evidence of association was found for rs11833579 in East Asian population as well as Chinese Han population.Journal of the neurological sciences 01/2012; 316(1-2):116-21. DOI:10.1016/j.jns.2012.01.010 · 2.26 Impact Factor
- [Show abstract] [Hide abstract]
ABSTRACT: With developments of etiology of cerebral small vessel disease (CSVD) and genome-wide association study (GWAS) of stroke, the genetic studies of CSVD are focused on genes related to blood-brain barrier (BBB) and aging. The project aims to investigate the association between CSVD and susceptibility loci and candidate genes. All study subjects admitted Beijing Tiantan Hospital from June 2009 to September 2010 including 197 cerebral small vessel disease patients(S), 198 large artery atherosclerosis control individuals (vascular stenotic rate ≥50% diameter reduction) (L), 200 hypertensive intracerebral hemorrhage control individuals (H) and 197 stroke-free control individuals (C). 15 SNPs in 4 genes (MYLK, AQP4, NINJ2, and INK4/ARF) were genotyped using Multiplex Snapshot assay. Each SNP was first examined between the groups S and C in different genetic models (codominant, dominant, recessive, overdominant, and log-additive). Permutation correction was used to adjust for multiple testing. The significant SNP loci were further analyzed in comparing S with L and H, respectively. Subgroup analysis was also performed for each risk-factor category. Among the 15 SNPs, rs2222823 and rs2811712 were found to be significantly associated with CSVD after multiple-testing adjustment. The heterozygote (A/T) of rs2222823 of MYLK has an odds ratio of 0.52 (95% CI =[0.35, 0.79], P= 0.002, adjusted P= 0.031) when compared with homozygotes. The heterozygote (C/T) of rs2811712 of INK4/ARF has an odds ratio of 1.75 (95% CI =[1.13-2.71], P= 0.004, adjusted P= 0.050). The SNP rs2222823 was significant (P= 0.035) in comparing S with H. In comparing S versus L, it is significant for the subgroups of patients without diabetes (P= 0.012) and drinking (P= 0.018). rs2811712 was significant in comparing S with L for the subgroups of patients with hyperlipidemia (P= 0.029) and drinking (P= 0.04). The heterozygotes (T/A) at the rs2222823 SNP locus of MYLK gene decreases the risk of having cerebral small vessel disease, while the heterozygotes (C/T) at the rs2811712 SNP locus of INK4/ARF gene increases the risk, suggesting that the MYLK and INK4/ARF are the associated genes of cerebral small vessel disease in Han Chinese population.CNS Neuroscience & Therapeutics 05/2012; 18(7):558-65. DOI:10.1111/j.1755-5949.2012.00322.x · 3.78 Impact Factor
- [Show abstract] [Hide abstract]
ABSTRACT: In 2009, a GWAS has confirmed that rs11833579 and rs12425791 near the NINJ2 gene could increase the stroke and ischemic stroke (IS) risk. Recently, several studies have been implemented to assess the relationship between the two SNPs and ischemic stroke risk in Asian. However, the results were poorly consistent. To study the association between the both polymorphisms and the risk of ischemic stroke, we performed a meta-analysis. We used odds ratios (ORs) with 95% confidence intervals (CIs) to evaluate the strength of association. The heterogeneity was checked by Q test and the inconsistency index (I(2)). Begg's test and Egger's test were used to assess the possible publication bias. Our study included 6 articles, contained 9 independent case-control studies, involved a total of 9,142 cases and 10,652 controls about rs11833579, 10,165 cases and 11,592 controls about rs12425791. There was a significant association between rs12425791 and IS risk with dominant genetic model (OR=1.087, 95%CI=1.021-1.158, I(2)=34.6%, P=0.152), but not with recessive genetic model and allele A vs. allele G. For rs11833579, we failed to verify it relate with IS risk under allele A vs. allele G, dominant and recessive genetic model. This meta-analysis suggest that rs12425791 is relative to ischemic stroke risk under dominant model in Asian population, but not for rs11833579.Thrombosis Research 07/2012; 130(3):e95-e102. DOI:10.1016/j.thromres.2012.06.014 · 2.43 Impact Factor