Association between genetic variant on chromosome 12p13 and stroke survival and recurrence: a one year prospective study in Taiwan

Abstract

BackgroundThe association between ischemic stroke and 2 single nucleotide polymorphisms (SNPs) on chromosome 12p13, rs12425791 and rs11833579 appears inconsistent across different samples. These SNPs are close to the ninjurin2 gene which may alter the risk of stroke by affecting brain response to ischemic injury. The purpose of this study was to investigate the association between these two SNPs and ischemic stroke risk, as well as prognostic outcomes in a Taiwanese sample.MethodsWe examined the relations of these two SNPs to the odds of new-onset ischemic stroke, ischemic stroke subtypes, and to the one year risk of stroke-related death or recurrent stroke following initial stroke in a case-control study. A total of 765 consecutive patients who had first-ever ischemic stroke were compared to 977 stroke-free, age-matched controls. SNPs were genotyped by Taqman fluorescent allelic discrimination assay. The association between ischemic stroke and SNPs were analyzed by multivariate logistic regression. Cox proportional hazard model was used to assess the effect of individual SNPs on stroke-related mortality or recurrent stroke.ResultsThere was no significant association between SNP rs12425791 and rs11833579 and ischemic stroke after multiple testing corrections. However, the marginal significant association was observed between SNP rs12425791 and large artery atherosclerosis under recessive model (OR, 2.30; 95%CI, 1.22-4.34; q-value = 0.062). Among the 765 ischemic stroke patients, 59 died or developed a recurrent stroke. After adjustment for age, sex, vascular risk factors and baseline stroke severity, Cox proportional hazard analysis indicated that the hazard ratios were 2.76 (95%CI, 1.34-5.68; q-value, 0.02) and 2.15 (95%CI, 1.15-4.02; q-value, 0.03) for individuals with homozygous variant allele of rs12425791 and rs11833579, respectively.ConclusionsThis is a precedent study that found genetic variants of rs12425791 and rs11833579 on chromosome 12p13 are independent predictors of stroke-related mortality or stroke recurrence in patients with incident ischemic stroke in Taiwan. Further study is needed to explore the details of the physiological function and the molecular mechanisms underlying the association of this genetic locus with ischemic stroke.

Association between the single-nucleotide polymorphism rs12425791 and ischemic stroke in Chinese populations: new data and meta-analysis

“…Our results are in agreement with three other studies [6,[13][14][15] carried out in Chinese populations, but inconsistent with three other studies [10][11][12]. The result of our study in the Guangxi Han population was inconsistent with a previous genome-wide association study in Caucasians [5].…”

“…In contrast, a significant association between rs12425791 and IS was found in a large populationbased case-control study in Japan [9]. Three studies [10][11][12] reported that rs12425791 was associated with IS risk in Chinese populations, whereas no evidence of association between rs12425791 and IS was found in three other studies [6,[13][14][15]. It seems that the association between rs12425791 and IS differs among different ethnic populations, including Chinese populations.…”

Diet regulates liver autophagy differentially in murine acute Trypanosoma cruzi infection

“…Autophagy plays a pivotal role not only in normal liver physiology, but also in the pathogenesis of many liver diseases including nonalcoholic and alcoholic fatty liver and viral hepatitis (Mao et al 2016; Tang et al 2012). Acute T. cruzi infection may adapt lipophagic pathway to survive energy starvation by increasing autophagic sequestration of lipid droplets and their degradation in hepatic lysosomes.…”

Guidelines for the Primary Prevention of Stroke

“…A meta-analysis of genome-wide association studies from prospective cohorts identified a locus on 12p13 near the NINJ2 gene associated with incident ischemic stroke, 71 but large case-control studies have not replicated this finding. 72,73 This inconsistency may be because of a possible effect of this locus on stroke mortality, 74 a synthetic association from rare variants not well represented in the subsequent replication studies, or a false-positive association. Recent meta-analyses of large case-control studies have identified novel genetic associations with specific stroke subtypes, suggesting that risk factor profiles and pathological mechanisms may differ across subtypes.…”