Kamali-Sarvestani Eskandar, Nikseresht Ali-Reza, Aliparasti Mohammad-Reza, Vessal Mahmood
Department of Immunology, Medical School, Shiraz University of Medical Sciences, Shiraz, Iran.
Neurosci Lett. 2006 Aug 14;404(1-2):159-62. doi: 10.1016/j.neulet.2006.05.033. Epub 2006 Jun 21.
IL-8 plays important roles in CNS development, modulation of neuronal survival and excitability. Among IL-8 receptors, only CXCR2 is known to be present in the brain. The ability of individuals in producing IL-8 is partially determined by IL-8 -251 A/T polymorphism. Therefore, the aim of the present study was to investigate the association between IL-8 -251 A/T and CXCR2 +1208 C/T gene polymorphisms and susceptibility to multiple sclerosis (MS). Two hundred and twenty-three MS patients and 319 healthy and ethnic matched controls were included in this study. IL-8 promoter (-251 A/T) and CXCR2 (+1208 C/T) gene polymorphisms were genotyped via allele specific PCR (AS-PCR) method. A significant difference was found in IL-8 -251 A/T polymorphism between MS patients and controls (p = 0.04). This deference was a result of a higher incidence of the low producer allele of IL-8 (T allele) in MS patients compared to controls. However, there was no significant association between different clinical findings (EDSS score, progression index, disease onset age, and the type of disease) and IL-8 -251 A/T polymorphism. Furthermore, no significant association existed between CXCR2 +1208 C/T polymorphism and MS susceptibility or different clinical parameters in patients. In summary, carriers of IL-8 -251 T allele may have increased susceptibility to MS because of their differences in neuron survival or increased chances of viral persistence compared to carriers of A allele.
白细胞介素-8(IL-8)在中枢神经系统发育、神经元存活调节和兴奋性调节中发挥着重要作用。在IL-8受体中,已知只有CXC趋化因子受体2(CXCR2)存在于大脑中。个体产生IL-8的能力部分由IL-8 -251 A/T多态性决定。因此,本研究的目的是调查IL-8 -251 A/T和CXCR2 +1208 C/T基因多态性与多发性硬化症(MS)易感性之间的关联。本研究纳入了223例MS患者以及319名健康且种族匹配的对照者。通过等位基因特异性PCR(AS-PCR)方法对IL-8启动子(-251 A/T)和CXCR2(+1208 C/T)基因多态性进行基因分型。在MS患者和对照者之间,发现IL-8 -251 A/T多态性存在显著差异(p = 0.04)。这种差异是由于与对照者相比,MS患者中IL-8低产生等位基因(T等位基因)的发生率更高。然而,不同临床指标(扩展残疾状态量表评分、进展指数、疾病发病年龄和疾病类型)与IL-8 -251 A/T多态性之间没有显著关联。此外,CXCR2 +1208 C/T多态性与MS易感性或患者的不同临床参数之间也没有显著关联。总之,与A等位基因携带者相比,IL-8 -251 T等位基因携带者可能由于神经元存活差异或病毒持续存在几率增加而对MS的易感性增加。