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The mitochondrial uncoupling protein 2 (UCP2) acts as an anion transporter and as an antioxidant factor able to reduce the reactive oxygen species level. Based on its effects, UCP2 prevents the membrane lipids, proteins, and DNA damage while preserving normal cellular functions. Many variants have been identified within the human UCP2. Some of them were associated with a higher risk of obesity, diabetes and cardiovascular diseases in different populations. UCP2 appears a suitable candidate also for the risk of ischemic stroke. In the current study, we investigated the possible association between few variants of UCP2 (rs659366, rs660339, rs1554995310) and the risk of ischemic stroke in a genetically homogenous cohort of cases and controls selected in Sardinia Island. This population has been previously analysed for other candidate genes. A total of 250 cases of ischemic stroke and 241 controls were enrolled in the study. The allelic/genotypic distribution of the 3 UCP2 variants was characterized and compared among cases and controls. The results of our study confirmed known risk factors for ischemic stroke: age, history of smoking, hypertension, hypercholesterolemia, and atrial fibrillation. No association was found between the 3 UCP2 variants and the risk of ischemic stroke in our Sardinian cohort. [ABSTRACT FROM AUTHOR]

Genetic factors contribute to the risk of ischemic stroke (IS). The phosphodiesterase-4D (PDE4D) and the 5-lipoxygenase activating protein (ALOX5AP) genes were identified as contributors to stroke in an Icelandic population. In an attempt to better define the contributory role of PDE4D and ALOX5AP genes to the risk of IS in humans, we carried out the present association study in a well-characterized, earlier published, genetically homogenous population from the island of Sardinia, Italy. In this cohort, including 294 cases and 235 controls, age, hypertension, hypercholesterolemia, and atrial fibrillation represent risk factors for IS. The PDE4D gene was evaluated by four single nucleotide polymorphisms (SNP32, SNP45, SNP83, SNP87) and by the microsatellite AC008818-1; the ALOX5AP gene was characterized by three SNPs (SG13S32, SG13S89, ALO2A). The results of our study provide no evidence of association between any single PDE4D and ALOX5AP gene variant with the risk of IS in the Sardinian cohort. Haplotype analysis, including that constructed with allele 0 of microsatellite AC008818-1 and SNP45 of the PDE4D gene, was also negative. In conclusion, we found no evidence of association between PDE4D and ALOX5AP genes and the risk of IS in a genetically homogenous population from Sardinia. [ABSTRACT FROM AUTHOR]

Background: β2-adrenergic receptors (β2-AR) mediate vasorelaxation in response to adrenergic agents. Genetic polymorphisms of β2-AR were implicated in various cardiovascular and noncardiovascular traits. Methods: We tested the role of the β2AR-16 and β2AR-27 gene variants in the susceptibility to the development of ischemic stroke in a genetically homogenous and clinically well-characterized case-control sample that included 294 cases and 286 controls from Sardinia, Italy. This population was shown to be an optimal study sample for carrying out genetic analyses. Results: Age, hypertension, dyslipidemia, and atrial fibrillation were independent risk factors for stroke in this cohort. We found that the presence of the Glu27 allelic variant was associated with a significantly increased risk of stroke when assuming a recessive mode of inheritance (odds ratio [OR], 1.68; 95% confidence interval [CI], 1.17–2.41; P = .005). The same results were obtained for the subgroup of ischemic strokes of arterial origin (n = 215): OR, 1.71; 95% CI, 1.14–2.57; P = .009. Furthermore, haplotype analysis confirmed that the presence of the Glu27 allele increased the risk of cerebrovascular accidents. Conclusions: Our data suggest that the Glu27 allelic variant of the β2-AR gene may be a determinant of ischemic stroke. [Copyright &y& Elsevier]

Background: Following an acute brain ischemia, local endothelia allow monocyte chemoattraction into the lesion site which contributes to brain damage through a group of neurotoxic factors. A relationship exists between the extent of brain damage and the plasma level of monocyte products, including chitotriosidase, though usually strictly related to preexisting infectious-inflammatory diseases. Purpose: Since chitotriosidase activity is also elevated in pathogen-free conditions, we tested whether chitotriosidase upregulation might be specifically related to stroke and unrelated to clinically relevant infectious diseases. Methods: We studied the plasma level of chitotriosidase activity, TNF-α and IL-6 in 44 consecutive patients with acute brain ischemia without concomitant symptoms or signs of inflammatory-infectious diseases. Results were compared with stroke severity and outcome as detected by brain CT and NIH scale. Blood samples were collected, on average, 11 h after stroke onset. Results: Chitotriosidase activity positively correlates with stroke severity, as measured by NIH scale (r = 0.69, p<0.01), to the extent of brain damage as documented by CT (r = 0.75, p ≤ 0.001) and the TNF-α level (r = 0.76, p<0.001); it also inversely correlates with the IL-6 level (r = –0.43, p ≤ 0.05). Conclusion: Our results indicate that chitotriosidase is a specific marker of macrophage activation occurring in stroke which directly correlates with stroke severity independently of preexisting inflammatory or infectious conditions. Copyright © 2005 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]