Ultimately, apart from genetic factors, there are different levels of vitamin B family and folic acid intake in the different regions and populations, which may cause inconsistent results. Although we did not measure the concentration of either homocysteine or vitamin B family and folic acid or derivatives, we speculate that the different levels of vitamin and folate intake do exist in different populations which may impact the results. Hypertension is a main risk factor for ischemic stroke and cerebral hemorrhage. Due to our matching criteria, cases and controls were matched by their blood pressure categories. The strategy was initially designed to increase the chance of finding genes predisposing to ischemic stroke and cerebral hemorrhage independent of blood pressure. In addition, it has been noted that in a large-scale prospective study, the A allele of NPPA rs5063 has provided a protective effect for blood pressure progression in 48 months and incident hypertension for the entire follow-up. Qian ea al, reported that in a meta-analysis that MTHFR rs1801133 was significantly associated with hypertension among both the European and East Asian adult population. In the present study, cases and controls were matched with blood pressure categories. To further rule out the BAY-60-7550 PDE inhibitor influence of NPPA rs5063 and MTHFR rs1801133 on blood pressure and subsequently on ischemic stroke and cerebral hemorrhage, we tested the interaction of NPPA rs5063 and MTHFR rs1801133 with hypertension status in control population, and we did not find any interaction with hypertension. We further individually tested the association of NPPA rs5063 and MTHFR rs1801133 with ischemic stroke and cerebral hemorrhage in the hypertension and non-hypertension groups and found that NPPA rs5063 was associated with both ischemic stroke and cerebral hemorrhage in the hypertension group, In non -hypertension group, the association between NPPA rs5063 and ischemic stroke and cerebral hemorrhage did not reach significance but the effect size and directions were the same as in hypertension group. MTHFR rs1801133 was associated with cerebral hemorrhage in both hypertension group and non-hypertension group. Therefore, we concluded that NPPA rs5063 and MTHFR rs1801133 were associated with cerebral hemorrhage and NPPA rs5063 was marginally associated with ischemic stroke and were not directly associated with hypertension. These results were derived from stratified cohorts, therefore, the sample size, alone with other factors may play a role in the significant association. Studies with greater sample size and in other population are needed to ascertain the associations. Many mental disorders including anxiety disorders such as specific phobia, panic disorder, post-traumatic disorder and mood disorders develop in early life stages ; the age of onset of anxiety disorders is earlier than those of other disorders. Importantly, there are notable individual differences in vulnerability, resilience and treatment response. For example, the Tokyo subway sarin attack in 1995 by a radical cult produced severe PTSD in some bystanders, but not to others. Gray-matter volume reductions in the left anterior cingulate cortex were observed only in the victims who developed PTSD.
The biological role of this variant may have some effect on the biological pathways of its involvement in stroke
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