Research Article| Volume 345, ISSUE 1-2, P198-201, October 15, 2014

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Association between 12p13 SNP rs11833579 and ischemic stroke in Asian population: An updated meta-analysis


      • 11 studies including 9358 ischemic stroke cases and 8936 controls were pooled.
      • SNP rs11833579 is not linked to ischemic stroke in the Asian population.
      • SNP rs11833579 is not associated with LAA or SAO stroke under four genetic models.



      A GWAS found that the single-nucleotide polymorphism rs11833579 near the NINJ2 gene on chromosome 12p13 was associated with an increased risk of ischemic stroke in Caucasians in 2009. Several studies have been carried out to explore the association between this SNP and ischemic stroke in Asians, but published results were contradictory. In the present study, we performed a meta-analysis to further evaluate this association in the Asian population.


      All relevant articles were retrieved from the databases of PubMed, EMBASE, Chinese Biomedical Literature Database, CNKI, CQVIP, and WANFANG Database from the establishment date to February 2014. Statistical analyses were performed by using Stata 11. The pooled odds ratios (ORs) with 95% confidence intervals (95% CIs) were used to assess the strength of the association. Possible publication bias was checked by funnel plots, Begg's test and Egger's test.


      Eleven studies were eligible for meta-analysis including 9358 cases and 8936 controls. Overall, there were no significant associations between rs11833579 and ischemic stroke under the allelic (OR = 0.963, 95% CI: 0.850–1.092, p = 0.559), dominant (OR = 0.946, 95% CI: 0.778–1.150, p = 0.580), recessive (OR = 0.993, 95% CI: 0.914–1.078, p = 0.868), and homozygote (OR = 0.968, 95% CI: 0.796–1.177, p = 0.744) genetic models in the Asian population. Further, we found no evidence of association of rs11833579 with large artery atherosclerosis (LAA) or small-artery occlusion (SAO) stroke in all genetic models. The results of the subgroup analysis for Chinese population and Japanese population were consistent with that of the overall study.


      Our meta-analysis shows that SNP rs11833579 is not related to ischemic stroke in the Asian population.


      OR (odds ratio), 95% CI (95% confidence interval), LAA (large artery atherosclerosis), SAO (small-artery occlusion), SNP (single-nucleotide polymorphism), Ninjurin2 (nerve injury induced protein 2), HWE (Hardy–Weinberg equilibrium)


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        • Sturmer T.
        • Schlindwein G.
        • Kleiser B.
        • Roempp A.
        • Brenner H.
        Clinical diagnosis of ischemic versus hemorrhagic stroke: applicability of existing scores in the emergency situation and proposal of a new score.
        Neuroepidemiology. 2002; 21: 8-17
        • Feigin V.L.
        • Lawes C.M.
        • Bennett D.A.
        • Anderson C.S.
        Stroke epidemiology: a review of population-based studies of incidence, prevalence, and case-fatality in the late 20th century.
        Lancet Neurol. 2003; 2: 43-53
        • Bevan S.
        • Traylor M.
        • Adib-Samii P.
        • Malik R.
        • Paul N.L.
        • Jackson C.
        • et al.
        Genetic heritability of ischemic stroke and the contribution of previously reported candidate gene and genomewide associations.
        Stroke. 2012; 43: 3161-3167
        • Ikram M.A.
        • Seshadri S.
        • Bis J.C.
        • Fornage M.
        • DeStefano A.L.
        • Aulchenko Y.S.
        • et al.
        Genomewide association studies of stroke.
        N Engl J Med. 2009; 360: 1718-1728
        • Araki T.
        • Milbrandt J.
        Ninjurin2, a novel homophilic adhesion molecule, is expressed in mature sensory and enteric neurons and promotes neurite outgrowth.
        J Neurosci Off J Soc Neurosci. 2000; 20: 187-195
        • Burgoon M.P.
        • Hazan R.B.
        • Phillips G.R.
        • Crossin K.L.
        • Edelman G.M.
        • Cunningham B.A.
        Functional analysis of posttranslational cleavage products of the neuron-glia cell adhesion molecule, Ng-CAM.
        J Cell Biol. 1995; 130: 733-744
        • Higgins J.P.
        • Thompson S.G.
        • Deeks J.J.
        • Altman D.G.
        Measuring inconsistency in meta-analyses.
        BMJ. 2003; 327: 557-560
        • Zhang Y.
        • Zhang J.
        • Huang J.
        • Li X.
        • He C.
        • Tian C.
        • et al.
        Polymorphisms in the transforming growth factor-beta1 gene and the risk of asthma: a meta-analysis.
        Respirology. 2010; 15: 643-650
        • Matsushita T.
        • Umeno J.
        • Hirakawa Y.
        • Yonemoto K.
        • Ashikawa K.
        • Amitani H.
        • et al.
        Association study of the polymorphisms on chromosome 12p13 with atherothrombotic stroke in the Japanese population.
        J Hum Genet. 2010; 55: 473-476
        • Ding H.
        • Tu X.
        • Xu Y.
        • Xu C.
        • Wang X.
        • Cui G.
        • et al.
        No evidence for association of 12p13 SNPs rs11833579 and rs12425791 within NINJ2 gene with ischemic stroke in Chinese Han population.
        Atherosclerosis. 2011; 216: 381-382
        • Chen K.
        • Xiao Z.S.
        • Hou S.Q.
        • Zhao R.T.
        • Liu Y.F.
        • Dou H.D.
        • et al.
        Strong association between the NINJ2 gene polymorphism and the susceptibility of stroke in Chinese Han population in Fangshan district.
        Beijing Da Xue Xue Bao. 2010; 42: 498-502
        • Hsieh Y.C.
        • Seshadri S.
        • Chung W.T.
        • Hsieh F.I.
        • Hsu Y.H.
        • Lin H.J.
        • et al.
        Association between genetic variant on chromosome 12p13 and stroke survival and recurrence: a one year prospective study in Taiwan.
        J Biomed Sci. 2012; 19: 1
        • Tong Y.
        • Zhan F.
        • Han J.
        • Zhang Y.
        • Yin X.
        • Geng Y.
        • et al.
        Lack of association between two key SNPs on chromosome 12p13 and ischemic stroke in Chinese Uyghur population.
        J Neurol Sci. 2012; 323: 52-55
        • Tong Y.
        • Zhang Y.
        • Zhang R.
        • Geng Y.
        • Lin L.
        • Wang Z.
        • et al.
        Association between two key SNPs on chromosome 12p13 and ischemic stroke in Chinese Han population.
        Pharmacogenet Genomics. 2011; 21: 572-578
        • Wang X.
        • Zhang J.
        • Liu Y.
        • Zhang Y.
        Relationship between nerve injury-induced protein gene 2 polymorphism and stroke in Chinese Han population.
        J Biomed Res. 2011; 25: 287-291
        • Shang X.-j.
        • Lin Y.
        • Fang L.
        • Cai B.
        • Wei W.
        • Wang N.
        Association analysis of two polymorphisms on chromosome 12p13 to cerebral infarction.
        Chin J Neurol. 2011; 44: 613-618
        • Adams Jr., H.P.
        • Bendixen B.H.
        • Kappelle L.J.
        • Biller J.
        • Love B.B.
        • Gordon D.L.
        • et al.
        Classification of subtype of acute ischemic stroke. Definitions for use in a multicenter clinical trial. TOAST. Trial of Org 10172 in Acute Stroke Treatment.
        Stroke. 1993; 24: 35-41
        • Li B.H.
        • Zhang L.L.
        • Yin Y.W.
        • Pi Y.
        • Guo L.
        • Yang Q.W.
        • et al.
        Association between 12p13 SNPs rs11833579/rs12425791 near NINJ2 gene and ischemic stroke in East Asian population: evidence from a meta-analysis.
        J Neurol Sci. 2012; 316: 116-121
        • Lian G.
        • Yan Y.
        • Jianxiong L.
        • Juanjuan X.
        • Qing C.
        • Guangliang W.
        • et al.
        The rs11833579 and rs12425791 polymorphisms and risk of ischemic stroke in an Asian population: a meta-analysis.
        Thromb Res. 2012; 130: e95-e102