Stojković Ljiljana, Stanković Aleksandra, Djurić Tamara, Dinčić Evica, Alavantić Dragan, Zivković Maja
Laboratory for Radiobiology and Molecular Genetics, VINČA Institute of Nuclear Sciences, University of Belgrade, P.O. Box 522, 11001, Belgrade, Serbia.
J Neurol. 2014 Aug;261(8):1544-51. doi: 10.1007/s00415-014-7379-7. Epub 2014 May 23.
CXC ligand 16 (CXCL16) is a multifunctional chemokine involved in cell adhesion and chemoattraction as well as in the scavenging of oxidized lipoproteins. Experimental data suggest the roles of CXCL16 in pathogenesis of multiple sclerosis (MS). A181V polymorphism in the human CXCL16 gene has been associated with the clinical course of certain chronic inflammatory diseases. The aim of this study was to analyze the effects of CXCL16 A181V polymorphism on: (1) susceptibility to MS and disease course, (2) peripheral blood mononuclear cells (PBMC) CXCL16 mRNA levels and plasma soluble CXCL16 levels of patients with MS and healthy controls. In this study, 459 MS patients and 303 controls were included. Real-time PCR-based methods were applied for genotyping of CXCL16 A181V and for CXCL16 gene expression analysis. Quantitative sandwich enzyme immunoassay was performed for quantification of plasma soluble CXCL16. CXCL16 AA genotype had a significant protective effect on MS susceptibility in women (OR = 0.53, ±95 % CI = 0.35-0.82, p = 0.004). The V allele-containing genotypes were associated with significantly higher CXCL16 mRNA levels in PBMC of both female (mean factor = 1.81, S.E. = 1.14-2.77, p < 0.01) and male (mean factor = 1.58, S.E. = 1.35-1.73, p < 0.01) controls. No significant association of the CXCL16 polymorphism was established either with soluble CXCL16 plasma levels or with clinical parameters and course of MS. The main finding of this study is gender-specific association of CXCL16 A181V polymorphism with susceptibility to MS in females. The current results should be replicated and validated in the larger sample group.
CXC趋化因子配体16（CXCL16）是一种多功能趋化因子，参与细胞黏附和趋化作用，以及氧化脂蛋白的清除。实验数据表明CXCL16在多发性硬化症（MS）的发病机制中发挥作用。人类CXCL16基因中的A181V多态性与某些慢性炎症性疾病的临床病程相关。本研究的目的是分析CXCL16 A181V多态性对以下方面的影响：（1）MS易感性和疾病病程；（2）MS患者和健康对照外周血单个核细胞（PBMC）中CXCL16 mRNA水平及血浆可溶性CXCL16水平。本研究纳入了459例MS患者和303例对照。采用基于实时PCR的方法对CXCL16 A181V进行基因分型，并分析CXCL16基因表达。采用定量夹心酶免疫测定法对血浆可溶性CXCL16进行定量。CXCL16 AA基因型对女性MS易感性具有显著保护作用（OR = 0.53，±95% CI = 0.35 - 0.82，p = 0.004）。含V等位基因的基因型与女性（平均因子 = 1.81，标准误 = 1.14 - 2.77，p < 0.01）和男性（平均因子 = 1.58，标准误 = 1.35 - 1.73，p < 0.01）对照PBMC中显著更高的CXCL16 mRNA水平相关。CXCL16多态性与可溶性CXCL16血浆水平、MS临床参数及病程均未建立显著关联。本研究的主要发现是CXCL16 A181V多态性与女性MS易感性存在性别特异性关联。目前的结果应在更大样本组中进行重复和验证。
