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      IVS4-14 A/G and IVS4-73 C/T polymorphisms in OLR1 gene in patients with ischemic cerebrovascular diseases.

      Genetic testing and molecular biomarkers
      Adult, Aged, Alleles, Alternative Splicing, Atherosclerosis, genetics, Brain Ischemia, blood, Case-Control Studies, Cerebrovascular Disorders, Female, Gene Frequency, Genetic Markers, Genetic Predisposition to Disease, Homozygote, Humans, Linkage Disequilibrium, Lipoproteins, LDL, Male, Middle Aged, Polymorphism, Single Nucleotide, Risk Factors, Scavenger Receptors, Class E, chemistry

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          Abstract

          Oxidized low-density lipoprotein (ox-LDL) plays a key role in the processes of atherogenesis, the major cause of myocardial infarction. Increased levels of ox-LDL relate to plaque instability in human coronary atherosclerotic lesions. Moreover, ox-LDL levels show a direct correlation to the severity of coronary syndromes. Most of these effects are mediated by the interaction of ox-LDL with its major receptor, named LOX-1, that is encoded by OLR1 gene. In the present study, we examined the prevalence of OLR1 gene polymorphisms, IVS4-14 A/G and IVS4-73 C/T, which regulate the expression of LOXIN, in patients with ischemic cerebrovascular diseases (ICVD). We studied 43 consecutive patients (males = 19; females = 24) aged 26 to 65 years. All the patients were from the same geographical area. They were affected by ICVD. The control group comprised 69 healthy blood donors, with age and sex comparable to those of the patients. The distribution of G/G genotype and A/G genotype was statistically significant between patients and controls (chi(2) = 5.87, p = 0.01 and chi(2) = 4.33, p = 0.04, respectively). These preliminary data would suggest that in ICVD patients the LOX-1 isoform that induces internalization of ox-LDL is more frequent and a cascade of events responsible for endothelial dysfunction and injury. LOX-1 might play a fundamental role in the initiation and progression of atherosclerosis and have a significant role in the pathogenesis of ICVD. Therefore, the patients with G homozygosity for IVS4-14 polymorphism and T homozygosity for IVS4-73 polymorphism have higher risk to develop ICVD. Future studies are warranted to assess whether the analysis of polymorphisms may be useful for the clinical approach to evaluate risk factors for atherosclerosis and related disorders.

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