CAJ | 학술논문

目的探讨2q33区段CD28及ICOS基因多态性与多发性硬化(MS)遗传易感性及病情严重程度的关系.方法以来自中国南方汉族人群的83名确诊MS患者(MS组)和110名非自身免疫性疾病患者及健康志愿者(对照组)为研究对象,外周静脉血提取DNA,利用PCR-RFLP技术、琼脂糖凝胶电泳技术分析检测扩增产物CD28及ICOS基因的多态性.免疫荧光双标记流式细胞学法检测2组患者外周静脉血淋巴细胞表面CD28及ICOS表达水平.结果 MS组ICOS-2394位点TT基因型频率明显高于对照组(33.7%vs10.9%),T等位基因频率明显高于对照组(56.0%vs30.9%),差异有统计学意义(P＜0.05).3个位点单核苷酸多态性间无明显联合效应.ICOS-2394多态位点TT基因型与原发进展型(PP)-MS发病相关,而CT基因型与继发进展型(SP)-MS发病无关.3个位点基因型及等位基因频率与MS急性期患病严重程度均无明显相关(P＜0.05).MS组外周血淋巴细胞表面CD28及ICOS的表达均明显高于对照组,差异有统计学意义(P＜0.05).结论中国南方汉族人群ICOS-2394位点多态性与MS发病相关,其中TT基因型与PP-MS发病相关,而CT基因型与SP-MS发病无关,提示该基因为MS的易感基因.CD28基因多态性与MS患病无关.
목적 탐토2q33구단CD28급ICOS기인다태성여다발성경화(MS)유전역감성급병정엄중정도적관계.방법 이래자중국남방한족인군적83명학진MS환자(MS조)화110명비자신면역성질병환자급건강지원자(대조조)위연구대상,외주정맥혈제취DNA,이용PCR-RFLP기술、경지당응효전영기술분석검측확증산물CD28급ICOS기인적다태성.면역형광쌍표기류식세포학법검측2조환자외주정맥혈림파세포표면CD28급ICOS표체수평.결과 MS조ICOS-2394위점TT기인형빈솔명현고우대조조(33.7%vs10.9%),T등위기인빈솔명현고우대조조(56.0%vs30.9%),차이유통계학의의(P＜0.05).3개위점단핵감산다태성간무명현연합효응.ICOS-2394다태위점TT기인형여원발진전형(PP)-MS발병상관,이CT기인형여계발진전형(SP)-MS발병무관.3개위점기인형급등위기인빈솔여MS급성기환병엄중정도균무명현상관(P＜0.05).MS조외주혈림파세포표면CD28급ICOS적표체균명현고우대조조,차이유통계학의의(P＜0.05).결론 중국남방한족인군ICOS-2394위점다태성여MS발병상관,기중TT기인형여PP-MS발병상관,이CT기인형여SP-MS발병무관,제시해기인위MS적역감기인.CD28기인다태성여MS환병무관.
Objective To investigate the polymorphisms of CD28 and COS genes in chromosome 2q33 region and susceptibility to and severity of multiple sclerosis (MS).Methods Eighty-three patients diagnosed as having MS from Han population of South China were studied; one hundred and ten patients with non-autoimmune diseases or healthy volunteers were selected as controls.DNA was obtained from peripheral venous blood; the polymorphisms of amplified productions (CD28 and ICOS genes) were detected by PCR-RFLP and analyzed by agarose gel electrophoresis.Immunofluorescent two-color flow cytometry was used to study the expressions of CD28 and ICOS genes of lymphocytes in the peripheral blood of these 2 groups. Results The genotype frequency of TT at ICOS-2394 site in patients with MS (33.7%) was significantly higher than that in controls (10.9%,P＜ 0.05), and the allele frequency of T in patient group (56.0%) was obviously higher than that in the controls (30.9%, P＜0.05). No marked combined effects were noted in the 3 SNPs (CD28-372, ICOS-2349 and ICOS-2119). TT genotype in the polymorphic site of ICOS-2394 was correlated to primary progressive MS, while CT genotype in the polymorphic site of ICOS-2394 was not correlated to secondary progressive MS. The genotype and allele frequencies of the 3 SNPs had no marked association with the severity of MS (P＞0.05). The levels of CD28 and ICOS gene expressions in lymphocytes of peripheral blood of patients with MS were significantly higher in patients than that in control group (P ＜ 0.05). Conclusion ICOS polymorphisms might be related to MS in Han population of South China,which suggests that ICOS might be one of genes having susceptibility to MS. No association between CD28 gene polymorphisms and susceptibility to MS is noted.