Scalabrini Diego, Fenoglio Chiara, Scarpini Elio, De Riz Milena, Comi Cristoforo, Venturelli Eliana, Cortini Francesca, Piola Mirko, Villa Chiara, Naldi Paola, Monaco Francesco, Bresolin Nereo, Galimberti Daniela
Department of Neurological Sciences, Dino Ferrari Center, University of Milan, IRCCS Ospedale Maggiore Policlinico, Milan, Italy.
Neurosci Lett. 2007 Oct 2;425(3):173-6. doi: 10.1016/j.neulet.2007.08.020. Epub 2007 Aug 17.
Recently, proteomic analysis in cerebrospinal fluid (CSF) from patients with MS identified four proteins which are present in MS but not in normal human CSF, including SPARCL1, an extracellular matrix-associated protein member of the SPARC family. One hundred eighty-six patients with MS and 185 age-matched controls were genotyped for A/G single nucleotide polymorphism (SNP) in exon 1 (rs1049539), C/G SNP in exon 4 (rs1049544), resulting in a substitution of an aspartate with an histidine, and A/G substitution in the exon 5 (rs1130643), leading to the substitution of alanine with threonine. No significant differences in either allelic or genotypic frequency of the three SNPs were found (P>0.05), even in stratifying MS patients according to the course of the disease. Stratifying according to gender, a trend towards a decreased frequency of the C/C genotype of the rs1049544 was observed in male patients as compared with male controls (30.2% versus 44.0%; P=0.217). Despite proteomic studies in CSF from MS patients suggested an important role for SPARCL1 in the development of the disease, SPARCL1 gene does not appear to act as susceptibility factor for MS in the population investigated here. However, the frequency of the C/C genotype of rs1049544 was decreased in male patients, possibly conferring a lower risk of developing MS in male population. Further studies are needed to clarify this issue.
最近，对多发性硬化症（MS）患者脑脊液（CSF）的蛋白质组学分析鉴定出四种在MS患者脑脊液中存在但在正常人类脑脊液中不存在的蛋白质，其中包括SPARCL1，它是SPARC家族中一种与细胞外基质相关的蛋白质成员。对186例MS患者和185例年龄匹配的对照进行了基因分型，检测第1外显子中的A/G单核苷酸多态性（SNP）（rs1049539）、第4外显子中的C/G SNP（rs1049544），该SNP导致天冬氨酸被组氨酸取代，以及第5外显子中的A/G替换（rs1130643），导致丙氨酸被苏氨酸取代。未发现这三个SNP的等位基因频率或基因型频率有显著差异（P>0.05），即使根据疾病病程对MS患者进行分层也是如此。按性别分层时，与男性对照相比，男性患者中rs1049544的C/C基因型频率有降低趋势（30.2%对44.0%；P=0.217）。尽管对MS患者脑脊液的蛋白质组学研究表明SPARCL1在疾病发展中起重要作用，但在此研究的人群中，SPARCL1基因似乎不是MS的易感因素。然而，男性患者中rs1049544的C/C基因型频率降低，这可能使男性人群患MS的风险较低。需要进一步研究来阐明这个问题。
