可诱导协同刺激分子、CD28、CD24基因多态性与多发性硬化的相关性

目的探讨可诱导协同刺激分子（ICOS）、CD28、CD24基因多态性与多发性硬化（multiple sclerosis，MS）遗传易患性的相关性。方法以来自中国汉族人群的83例确诊MS患者和110例非自身免疫性疾病的患者及健康志愿者为研究对象，利用聚合酶链．限制性长度多态性分析（PCR-RFLP）技术检测3个基因扩增产物酶切多态性。结果ICOS-2394位点TT基因型频率MS组明显高于对照组（分别为33．7％和10．9％，P〈0．01），携带T等位基因可增加MS患病危险性（OR=3．482，P〈0．01）；ICOS-2119位点携带C-等位基因MS组明显低于对照组（分别为4．8％和15．5％，P〈0．05）。CD28-372位点基因型等位基因频率分布MS组与对照组差异无统计学意义。CD24 E2＋226位点T等位基因频率MS组较对照组增多（分别为44．6％和33．2％，P〈0．05）。单倍体型关联分析显示CD24 E2＋226T等位基因分别与ICOS-2394T及ICOS-2119C联合可明显增加MS患病危险性，CD28基因多态与ICOS基因多态构成的单体型在MS和对照组中差异无统计学意义。结论中国汉族人群ICOS-2394C／T、ICOS-2119C／T及CD24E2＋226C／T多态性与Ms发病相关，两基因可能均是MS的易患基因或与易患基因相连锁。CD28-372位点多态性与MS患病无直接相关。

The association between the inducible costimulatory molecules, CD28, CD24 gene polymorphisms and multiple sclerosis

Objective To investigate the relationship between the gene polymorphism of the inducible costimulatory molecules (ICOS),CD_(28),CD_(24) and susceptibility to multiple sclerosis(MS). Methods 83 patients with MS and 110 controls selected from healthy individuals and hospital staff in Chinese Han people with non-autoimmune diseases were studied by detecting genotype of the 3 genes using PCR-RFLP method. Results The frequency of ICOS-2394 TT genotypes was significantly higher in MS patients than in controls (MS 33.7%vs controls 10.9%, P<0.01), and the MS patients had an increase in the carrier frequency of the T allele (OR=3.482, P<0.01). ICOS-2119 C allele was significantly lower in MS patients than in controls (MS 4.8% vs controls 15.5%, P<0.05). The CD_ 28 -372 polymorphism revealed no significant differences of genotype and allele distribution in MS patients and controls. There showed a significant increase in the CD_ 24 E2+226 T allele frequency in MS patients as compared with the controls (MS 44.6% vs controls 33.2%, P<0.05).The haplotype related analysis showed that the interaction of the CD_ 24 E2+226 T allele and the ICOS-2394T/-2119C allele would increase the risk of MS. There was no significant interaction between the polymorphisms of CD_ 28 and ICOS in MS patients as compared with the controls. Conclusions ICOS-2394C/T, -2119C/T and CD_ 24 E2+226C/T polymorphisms are related with MS in Chinese Han people, either ICOS or CD_ 24 or both being one of the genes susceptible to MS or linking with susceptible genes. CD_ 28 -372A/G polymorphisms are not related with MS in Han people of China.