Plasma proteomics reveals coagulation, inflammation, and metabolic shifts in H-type hypertension patients with and without acute ischemic stroke.

Systematic profiling of a larger portion of circulating plasma proteome provide opportunities for unbiased discovery of novel markers to improve diagnostic, therapeutic, or predictive accuracy. This study aimed to identify differentially expressed proteins (DEPs) in plasma that could provide overall insight into the molecular changes of both H- type hypertension (HH) and HH-related acute ischemic stroke (AIS). This study used an iTRAQ-based LC-MS/MS proteomics approach to screen for plasma DEPs in HH patients with and without AIS, and controls. After excluding highly abundant plasma proteins, more than 600 proteins, and their relative levels, were identified. Of these, 26 DEPs, each showing > 1.2-fold change, were identified in HH and HH-related AIS patients compared with controls. Bioinformatics analysis revealed that these DEPs were enriched in 21 functional gene ontology items; "blood coagulation" was the most predominant pathway showing enrichment. Of these, eight DEPs were located in the hub position of networks involved with protein-protein interactions. AT-3, CRP, ApoB, and AHSG were further validated in each group by enzyme-linked immune sorbent assays. Comparing HH-related AIS with HH, the areas under the curve for AT-3, CRP, ApoB, and AHSG were 0.698, 0.892, 0.626, and 0.847, respectively. This proteomic profiling study provided enhanced pathophysiological understanding of the regulatory processes involved in coagulation, inflammation, and metabolism, and identified a panel of novel biomarkers for detecting HH-related AIS during its pre-stroke stage.

Methylenetetrahydrofolate reductase gene A1298C polymorphism and gene-environment interactions are associated with carotid plaque in a south Chinese population.

OBJECTIVE: Our primary objective was to evaluate the associations of conventional risk factors and methylenetetrahydrofolate reductase (MTHFR) gene polymorphisms with the risk of carotid plaque in a south Chinese population. Our secondary objective was to explore gene-environment interactions and potential relationship with carotid plaque. METHOD: We enrolled 229 patients suffer from carotid plaque and 180 controls in this case-control study. We measured the carotid intima-media thickness by ultrasound and investigated conventional risk factors, biomarkers and C677T/A1298C MTHFR genotypes. Logistic analysis was used to evaluate the association between conventional risk factors and carotid plaque. The SNPstats platform was used to investigate the association between MTHFR gene polymorphisms and carotid plaque under 5 genetic models (dominant, recessive, codominant, over dominant and additive models). Gene-environment interactions analysis was then performed by multifactor dimensionality reduction. RESULTS: Age and hypertension were identified as independent risk factors of carotid plaque. C677T and A1298C demonstrated associations with carotid plaque under the recessive model (C677T: P = 0.03, odds ratio = 3.14, 95% confidence interval = 1.04-11.21; A1298C: P = 0.018, odds ratio = 2.40, 95% confidence interval = 1.13-5.10). Neither C677T nor A1298C polymorphism was associated with stable or vulnerable plaques. Additionally, Significant multiplicative and additive interactions were observed in terms of carotid plaque between A1298C polymorphism and diabetes, age, and smoking (P = 0.013). CONCLUSION: MTHFR gene C677T and A1298C polymorphisms may act as modifiers of carotid plaque risk in south Chinese population. In addition, the combined effect of gene-environment interactions between A1298C polymorphism and conventional risk factors may promote the progression of carotid plaque.

ZNF208 polymorphisms associated with ischemic stroke in a southern Chinese Han population.

BACKGROUND: Ischemic stroke is one of the most common diseases with a high burden of neurological deficits, disability and death. Zinc finger protein 208 (ZNF208) was found to be involved in coronary heart disease, although little information is available about its association with ischemic stroke. We performed the present case-control study to clarify the association between single-nucleotide polymorphisms (SNPs) within ZNF208 and the risk of ischemic stroke in a southern Chinese Han population. METHODS: A total of 799 subjects (400 cases and 399 healthy controls) were enrolled in the present study. Five SNPs within ZNF208 gene were selected and genotyped using Sequenom MassARRY technology (Sequenom, Inc., San Diego, CA, USA). Data management and statistical analyses were conducted using Sequenom Typer, version 4.0, and a chi-squared test, as well as unconditional logistic regression. RESULTS: Statistical results showed that three variants were associated with the risk of ischemic stroke under allele models (rs2188971, rs2188972, rs8103163 and rs7248488). The variant rs2188972 was also associated with the risk of ischemic stroke in a recessive model after adjustment for age and sex. Haplotype analysis suggested that a significant difference existed between the Ars2188972 Trs2188971 Ars8103163 Ars7248488 haplotype and the risk of ischemic stroke, although this disappeared after adjustment for sex and age. CONCLUSIONS: The results obtained in the present study indicate a potential association between ZNF208 variants and the risk of ischemic risk in a southern Chinese Han population.