Association between two key SNPs on chromosome 12p13 and ischemic stroke in Chinese Han population.

School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Pharmacogenetics and Genomics (Impact Factor: 3.61). 09/2011; 21(9):572-8. DOI: 10.1097/FPC.0b013e32834911d0
Source: PubMed

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.

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    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.
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