Studies in different populations have shown that ischemic stroke can trigger an acute phase response resulting in a rise of plasma concentration of C-reactive protein (CRP). However, there are very limited studies on CRP and first ischemic stroke divided into subtypes. High levels of CRP may also be associated with poor outcome. The present study was taken up to investigate the prognostic value of CRP within 24 h of onset of ischemic stroke. Five hundred and eighty one patients with first stroke and 575 age- and sex-matched healthy controls were involved in the study. High-sensitivity C-reactive protein (hsCRP) levels were estimated, and follow-up interviews were conducted with patients at 3, 6, and 12 months post-event to determine stroke outcome. In addition to this plasma, NO( x ) (nitrate and nitrite) was measured to detect the serum NO (an important biomarker of inflammation and oxidative stress) levels in ischemic stroke patients and controls. The relationship between CRP value and poor outcome (>2 on modified Rankin Scale Score and <5 on an extended Glasgow outcome scale) was studied. There was a significant association between elevated levels of CRP and NO with the disease. A stepwise multiple logistic regression analysis confirmed these findings after adjustment for potential confounders [adjusted odds ratio = 2.890, 95% CI (1.603-5.011) with p < 0.01 and adjusted odds ratio = 2.364, 95% CI (1.312-3.998) with p < 0.01 for hsCRP and NO, respectively]. After adjustment of potential confounders, patients with high CRP levels had a significant increased risk of poor outcome [adjusted odds ratio = 3.50, 95% CI (1.312-6.365) and p < 0.001]. Elevated levels of hsCRP associated significantly with all stroke subtypes classified according to Trial of ORG 10172 in Acute Stroke Treatment classification except for lacunar stroke and stroke of other determined etiology. In conclusion, hsCRP and NO levels predict the incidence of ischemic stroke and hsCRP is an independent prognostic factor of poor outcome at 3 months.
Genetic variants of cytochrome P450 4F2 (CYP4F2) gene have been suggested to be risk factors for hypertension, cardiovascular diseases and stroke. In the present case-control study we investigated the association of 1347 G/A polymorphism (rs2108622) in the 11th exon region of CYP4F2 gene with hypertension, ischemic stroke and stroke subtypes classified according to TOAST (Trial of Org 10172 in Acute Stroke Treatment) classification. Five hundred and seven stroke patients (hypertensives: normotensives = 279:228) and four hundred and eighty seven, age and sex matched controls (males: females = 356:131) (hypertensives: normotensives = 148:339) were involved in the study. The genotypes were determined by PCR-RFLP technique. Genotypes were confirmed by subjecting the PCR products to sequencing. Significant difference was observed in the genotypic distribution and allelic frequency between the stroke patients and healthy controls. AA genotype and A allele associated significantly with stroke and hypertension [P = 0.009; OR = 1.59 (95% CI = 1.119-2.283) and P = 0.010; OR = 1.26 (95% CI = 1.056-1.502); P = 0.01; OR = 1.58 (95% CI = 1.11-2.272) and P = 0.010; OR = 1.25(95% CI = 1.054-1.504) respectively]. A stepwise logistic regression analysis confirmed these findings. To establish that this polymorphism is associated with stroke independent of hypertension; we compared stroke patients without hypertension with normotensive controls. Significant difference was observed in genotypic distribution and allelic frequency between the two groups (P = 0.001 and 0.002 respectively). Evaluating the association of this polymorphism with stroke subtypes we found significant associations with cardioembolic stroke (P < 0.001). In conclusion our study suggests that 1347A allele of CYP4F2 gene is an important risk factor for hypertension and ischemic stroke.
TNF-α +488 G/A variant is an important risk factor for ischemic stroke in the South Indians from Andhra Pradesh, whereas MMP-3-1612 5A/6A polymorphism is not associated with stroke in the same population.
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