Vietri Maria Teresa, Molinari Anna Maria, Boggia Maria, Parisi Mariarita, Cioffi Michele
Department of General Pathology, Second Medical School of Naples, Naples, Italy.
Genet Test Mol Biomarkers. 2010 Feb;14(1):9-11. doi: 10.1089/gtmb.2009.0101.
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.
氧化型低密度脂蛋白（ox-LDL）在动脉粥样硬化形成过程中起关键作用，动脉粥样硬化是心肌梗死的主要原因。ox-LDL水平升高与人类冠状动脉粥样硬化病变中的斑块不稳定性有关。此外，ox-LDL水平与冠状动脉综合征的严重程度直接相关。这些作用大多是由ox-LDL与其主要受体（名为LOX-1，由OLR1基因编码）相互作用介导的。
在本研究中，我们检测了缺血性脑血管疾病（ICVD）患者中调控LOXIN表达的OLR1基因多态性IVS4-14 A/G和IVS4-73 C/T的发生率。我们研究了43例年龄在26至65岁之间的连续患者（男性19例；女性24例）。所有患者来自同一地理区域。他们患有ICVD。对照组由69名健康献血者组成，年龄和性别与患者相当。
患者和对照组之间G/G基因型和A/G基因型的分布具有统计学意义（分别为χ² = 5.87，p = 0.01和χ² = 4.33，p = 0.04）。
这些初步数据表明，在ICVD患者中，诱导ox-LDL内化的LOX-1异构体更为常见，并且存在一系列导致内皮功能障碍和损伤的事件。LOX-1可能在动脉粥样硬化的发生和发展中起重要作用，并在ICVD的发病机制中起重要作用。因此，IVS4-14多态性为G纯合子且IVS4-73多态性为T纯合子的患者发生ICVD的风险更高。有必要进行进一步研究，以评估多态性分析是否有助于临床评估动脉粥样硬化及相关疾病的危险因素。
