细胞毒T淋巴细胞相关抗原4基因多态性与溃疡性结肠炎

目的炎症性肠病的发病与T细胞过度活化有关,细胞毒T淋巴细胞相关抗原4（CTLA-4）是重要的T细胞活化负性调节因子.本课题研究CTLA-4基因启动子区-1722位点（T/C）及-1661位点（A/G）多态性与中国汉族人群中溃疡性结肠炎（UC）的相关性.方法采用PCR-限制性片段长度多态性方法,对87例中国汉族UC患者和116例正常对照者进行CTLA-4基因-1722位点和-1661位点多态性检测.结果UC患者CTLA-4基因-1661位点A/G＋G/G基因型频率,-1661位点G等位基因频率显著高于正常对照组（34.5%比15.5%,P=0.002,OR=2.865,95%CI=1.467～5.596;19.0%比8.2%,P=0.002,OR=2.624,95%CI=1.435～4.796）;而在-1722位点的基因型频率、等位基因频率与对照组比较差异无统计学意义（P＞0.05）.结论CTLA-4基因启动子区-1661位点G等位基因与中国汉族UC存在显著相关性.     

溃疡性结肠炎患者中肿瘤坏死因子相关凋亡诱导配体基因多态性及单倍型分析

目的 探讨肿瘤坏死因子相关凋亡诱导配体(Trail)基因多态性及单倍型与溃疡性结肠炎(UC)的关系.方法 收集UC患者331例,健康对照者832名,PCR扩增Trail目的基因后,直接测序检测Trail基因3非编码区(G1525A/G1588A/C1595T)三种单核苷酸多态性,并分析Trail单倍型与UC的关系.结果 与对照组相比较,Trail G1525A突变等位基因A和基因型GA+ AA的频率在UC组中明显降低(P值均＜0.01);UC组Trail G1588A和C1595T两位点突变等位基因A和T的频率明显低于对照组,且差异有统计学意义(P值均＜0.01).轻和中度UC患者Trail C1595T突变等位基因T和CT+ TT基因型频率为49.15％和64.51％,重度UC患者分别为72.37％和84.21％,两组比较差异均有统计学意义(OR值分别=2.710和2.935,95％CI:1.598～4.596和1.188～7.249,P值均＜0.05).重度UC患者Trail G1525A突变等位基因A的频率为48.69％,较轻和中度UC患者(35.16％)增加(OR=1.750,95％CI:1.082～2.830,P=0.021).UC组中AAT单倍型频率显著低于对照组(43.09％比58.41％,95％CI:1.549～2.229,P＜0.01);GAT单倍型频率在UC组中明显增高(10.15％比0.18％,95％CI:0.005～0.051,P＜0.01).结论 Trail基因多态性及单倍型与UC易感性密切相关.     

溃疡性结肠炎患者和人类白细胞抗原-DQA1基因关联的研究

目的研究广东地区汉族人人类白细胞抗原-DQA1(HLA-DQA1)基因与溃疡性结肠炎(UC)的遗传关联.方法应用HLA基因聚合酶链反应-限制性片段长度多态性核苷酸分型技术,以等位基因特异性的限制性内切酶(ApalⅠ、BsajⅠ、HphⅠ、FokⅠ、MboⅡ、MnlⅠ)消化DQA1座位特异的PCR扩增产物,对60例UC患者和60例对照组的HLA-DQA1等位基因进行分析.结果 UC患者HLA-DQA1*0301等位基因频率(0.50)与对照组(0.19)比较,差异有显著性(P=0.0029,RR=5.881,Pc=0.023).结论 HLA-DQA1*0301与溃疡性结肠炎有一定关联,溃疡性结肠炎患者与正常人之间存在着免疫遗传异质性的差异.     

细胞毒性T淋巴细胞相关抗原4基因微卫星多态性与炎症性肠病的关系

目的探讨细胞毒性T淋巴细胞相关抗原4（CTLA-4）基因微卫星多态性与浙江省炎症性肠病（IBD）患者的相关性。方法对118例无血缘关系的IBD患者（99例溃疡性结肠炎，19例克罗恩病）以及140例正常对照者，采用特异性等位基因PCR方法，检测CTLA-4外显子4的3′非翻译区包含（AT）。重复序列的等位基因。扩增产物用12％非变性聚丙烯酰胺凝胶电泳，硝酸银染色。结果CTLA-4微卫星共有20种等位基因。与正常对照组比较，122bp等位基因频率在溃疡性结肠炎患者（P=0.0001／Pc=0．0025，OR=11.393，95％CI：2．574～50．429）和克罗恩病患者（P=0．0003／Pc=0.0050，OR=21.061，95％CI：3，927～112．94）中均显著增高。结论CTLA-4基因微卫星多态性与浙江省IBD患者显著相关。     

过氧化物酶体增殖活化受体γ基因Pro12Ala和C161T多态性与溃疡性结肠炎的相关性

目的研究过氧化物酶体增殖活化受体γ（PPAR-γ）基因Pro12Ala和C161T位点的多态性与湖北汉族人群溃疡性结肠炎（UC）的相关性。方法采用多聚酶链式反应-限制片段长度多态性分析方法（PCR-RFLP）,对212例UC患者和220例健康对照者进行PPAR-γ基因分型。结果UC患者PPAR-γ基因C161T位点C／T基因型频率,T等位基因频率明显高于正常组（35．4％比25．0％,P=0．015,OR=1．69,95％CI=1．12～2．57;20．1％比12．9％,P=0．006,OR=1．68,95％CI=1．17～2．43）,T等位基因携带者也高于正常对照组（37．7％比25．5％,P=0．007,OR=1．77,95％CI=1．18～2．68）。而Pro12Ala位点基因型频率,等位基因频率UC组与对照组比较差异无统计学意义（P〉0．05）。结论PPAR-γ基因C161T位点基因T等位基因与湖北汉族人群UC的发生存在相关性。     

江苏汉族人群白细胞介素-23受体基因多态性与炎症性肠病及其表型的关系

目的 探讨江苏汉族人群中IL-23受体基因多态性与炎症性肠病及其表型的关系.方法 选取178例炎症性肠病患者[溃疡性结肠炎(UC) 135例,克罗恩病(CD)43例]和134例健康对照,检测IL-23受体基因的6个单核苷酸多态性位点(rs1 1805303、rs1343151、rs11465804、rs11209032、rs17375018、rs11465788)的基因多态性,分析其与UC、CD各临床表型的关联性.结果 rs 11805303的T等位基因频率在UC中为60.4％,高于对照组(50.4％),P=0.020.UC的基因-表型分析显示,rs17375018位点的基因多态性与结肠炎活动性指数(UCDAI)即UC的严重程度相关,携带等位基因G的患者倾向于发生轻度UC.CD的基因-表型分析显示,rs17375018位点的A等位基因频率在诊断年龄≤25岁的CD患者中明显高于诊断年龄＞25岁的患者(41.7％比22.0％,P=0.050,OR=2.532,95％ CI0.988～6.494);rs11805303位点的基因型与CD的诊断年龄、病变范围有关联性(P值分别为0.039和0.044);rs 17375018位点的A等位基因携带者发生肠外表现的几率较等位基因G携带者低(23.1％比46.7％,P=0.040,OR =2.917,95％ CI1.027～8.283).结论 在江苏汉族人群中,rs11805303是UC的易感基因位点,同时rs11805303、rs17375018位点的基因多态性与UC、CD的临床表型有关联性.     

血管紧张素转换酶基因多态性与主动脉瘤易感性的荟萃分析

目的通过荟萃分析探讨血管紧张素转换酶(ACE)基因插入/缺失(I/D)多态性与主动脉瘤易感性的关系。方法计算机检索Cochrane Library、Elsevier ScienceDirect、PubMed/Medline、万方数据知识服务平台、中国知网、维普期刊资源整合服务平台,搜索已发表的关于ACE基因多态性与主动脉瘤的病例对照研究,检索时限为建库至2018-08-01。按Cochrane系统评价方法筛选文献、提取资料并评价质量后,采用Stata 15软件进行荟萃分析。结果最终纳入17篇文献,其中病例组4597例,对照组6407例。荟萃分析结果显示,ACE基因I/D多态性与主动脉瘤发病存在相关性。等位基因分析显示,ACE基因I/D多态性与主动脉瘤发病相关(OR=1.41,95%CI 1.21～1.65,P0.001),亚组分析中,亚洲人亚组OR=1.69 (95%CI 1.18～2.41,P=0.004),高加索人亚组OR=1.34(95%CI 1.14～1.56,P0.001);腹主动脉瘤亚组OR=1.25(95%CI 1.06～1.49,P=0.01),胸主动脉瘤亚组OR=1.59(95%CI 1.10～2.29,P=0.014),主动脉瘤亚组OR=2.03(95%CI 1.66～2.48,P0.001),主动脉夹层亚组OR=1.70(95%CI 1.18～2.45,P=0.004)。隐性基因模型(II+DI比DD)分析显示,ACE基因I/D多态性与主动脉瘤发病相关(OR=1.55,95%CI 1.20～2.01,P=0.001),在隐性模型亚组分析中,亚洲人亚组OR=2.44(95%CI 1.39～4.29,P=0.002),高加索人亚组OR=1.34(95%CI 1.05～1.69,P=0.017);腹主动脉瘤亚组OR=1.31(95%CI 0.99～1.73,P=0.058),胸主动脉瘤亚组OR=1.33(95%CI 0.85～2.07,P=0.206),主动脉瘤亚组OR=3.72(95%CI 2.75～5.03,P0.001),主动脉夹层亚组OR=2.13(95%CI 1.22～3.71,P=0.008)。显性模型(DD+DI比II)分析显示,ACE基因I/D多态性与主动脉瘤发病相关(OR=1.52,95%CI 1.28～1.81,P0.001),在显性模型亚组分析中,亚洲人亚组OR=1.39(95%CI 0.97～1.99,P=0.07),高加索人亚组OR=1.57(95%CI 1.28～1.94,P0.001);腹主动脉瘤亚组OR=1.35(95%CI 1.10～1.65,P=0.005),胸主动脉瘤亚组OR=2.42(95%CI 1.70～3.46,P0.001),主动脉瘤亚组OR=1.29(95%CI 0.94～1.79,P=0.119),主动脉夹层亚组OR=1.72(95%CI 1.31～2.28,P0.001)。结论总体上ACE基因I/D多态性与主动脉瘤发病存在相关性,为主动脉瘤的发病危险因素。在隐性模型胸主动脉瘤亚组和腹主动脉瘤亚组,显性模型亚洲人亚组、主动脉瘤亚组中,ACE基因I/D多态性与主动脉瘤相关性无统计学意义,还需要进一步研究验证。     

老年高血压患者血管紧张素转换酶和醛固酮合酶基因多态性与肾素血管紧张素醛固酮的关系

目的分析老年高血压晨峰患者血管紧张素转换酶(ACE)基因I/D、醛固酮合酶(CYP11B2)基因-344C/T多态性与肾素-血管紧张素-醛固酮系统(RAAS)的相关性。方法选择2016年2月~2017年12月云南省第一人民医院老年病科门诊及住院的老年原发性高血压患者200例,根据清晨血压水平分为晨峰增高组58例和非晨峰增高组142例。分析2组患者ACE基因I/D、CYP11B2基因-344C/T多态性和血浆RAAS参数的差异。结果 2组ACE基因型和等位基因频率比较,差异有统计学意义(χ^2=38.020,P=0.000;χ^2=42.040,P=0.000)。2组CYP11B2基因型和等位基因频率比较,差异无统计学意义(χ^2=0.261,P=0.878;χ^2=0.198,P=0.656)。晨峰增高组DD+TC、DD+TT基因型比例明显高于非晨峰增高组,差异有统计学意义(22.4%vs 3.5%,12.1%vs 2.1%,P<0.01);晨峰增高组II+TT、II+TC基因型比例明显低于非晨峰增高组,差异有统计学意义(13.8%vs 29.6%,P<0.05;5.2%vs 22.5%,P<0.01)。晨峰增高组血浆肾素、血管紧张素Ⅱ和醛固酮水平明显高于非晨峰增高组,差异有统计学意义(P<0.05,P<0.01)。logistic回归分析显示,DD+CC、DD+TC、DD+TT、肾素、血管紧张素Ⅱ为血压晨峰的重要影响因素(OR=8.084,95%CI:1.261~51.832,P=0.027;OR=14.459,95%CI:3.804~54.964,P=0.000;OR=9.753,95%CI:2.255~42.181,P=0.002;OR=1.816,95%CI:1.258~2.620,P=0.001;OR=0.634,95%CI:0.437~0.921,P=0.017)。结论 ACE基因DD型、肾素、血管紧张素Ⅱ是血压晨峰形成的主要影响因素。     

APEX1和OGG1基因多态性与结肠癌发病风险、肿瘤分期和预后转归的相关性

目的 调查APEX1和OGG1基因多态性与结肠癌发病风险、肿瘤分期和预后转归的相关性。方法 筛选保定市第一中心医院2019年2月至2021年12月诊断为结肠癌的160例患者的标本作为结肠癌组,同期收集我院160名健康个体的标本作为对照组。流行病学调查表收集个人数据;通过聚合酶链反应-限制性片段长度多态性(PCR-RFLP)对APEX1基因中的多态性(ASP/Glu)和OGG1基因中的多态性进行基因分型(Ser/Cys);按性别,年龄,饮酒和吸烟情况对APEX1基因多态性SNP分析。结果 ASP/Glu基因型与结肠癌正相关(OR=3.45;95%CI=1.32～5.87,P=0.003)。Glu/Glu基因型也与结肠癌相关(OR=3.87;95%CI=1.48～6.43,P=0.004)。结肠癌组患者和对照组中等位基因频率不同,Glu等位基因的携带者增加了结肠癌的风险(OR=1.85; 95%CI=1.24～4.22,P=0.014)。Ser/Cys基因型与结肠癌正相关(OR=2.85; 95%CI=1.64～4.27,P=0.001)。Cys/Cys基因型也与结肠癌相关(OR=3.22...     

热休克蛋白70-hom基因多态性与老年脑梗死易感性的研究

目的探讨热休克蛋白70(Hsp70)-hom基因多态性与老年脑梗死和高血压发生的关系。方法选择住院和门诊的老年患者220例,按诊断分为脑梗死组105例和高血压组115例,脑梗死组又分为单纯组38例和合并组67例,同期选取健康体检者100例为健康组。采用PCR-RFLP方法检测Hsp70-hom+2437位点基因多态性。结果与健康组比较,脑梗死组Hsp70 hom TT基因型及T等位基因明显升高,分别达到70.48%和82.38%(OR=3.311,95%CI:2.078～4.359,P=0.000;OR=2.121,95%CI:1.271～3.325,P=0.003)。与健康组比较,合并组、单纯组C与T等位基因频率有显著差异(OR=1.193,95%CI:1.128～3.246,P<0.05;OR=2.31 2,95%CI1.128～4.721,P<0.05)。结论 Hsp70 hom基因多态性与脑梗死易感性有关,Hsp70 hom+2437位点基因型的检测价值,值得进一步探讨。     

溃疡性结肠炎的白细胞介素(IL)-1β、IL-1受体拮抗剂、IL-4基因多态性

目的研究溃疡性结肠炎(UC)病人的白细胞介素(IL)-1β、IL-1受体拮抗剂(IL-1RA)、IL-4基因多态性,并分析其与抗中性粒细胞胞质抗体(ANCA)及临床分型的关系.方法用PCR-限制性片段长度多态性方法和序列特异性引物-PCR方法分别对81例UC病人和114例健康者进行IL-1β和IL-1RA、IL-4基因多态性分析.结果 UC组IL-4 的RP2基因频率明显高于对照组(29.0% 对11.8%,P=0.000 02),而对照组RP1基因频率明显高于UC组(88.2% 对71.0%,P=0.000 02),UC组RP1.2、RP2.2基因型的优势比值分别为2.71 (95%CI, 1.39～5.31),9.04 (95%CI, 1.05～203.29);2组IL-1β、IL-1RA各基因频率比较差异均无显著性 (P＞0.05);ANCA(+)组和ANCA(-)组UC病人IL-4的 RP1、RP2基因频率显著不同,差异有显著性 (P值均<0.05).结论中国汉族UC病人与IL-4内含子3的基因多态性相关联,UC病人IL-4 RP1基因频率明显降低,而RP2基因频率明显增加,与正常人的差异发生在 ANCA(+) UC病人;中国汉族UC病人与IL-1β、IL-1RA基因多态性无关联.     

新疆地区维吾尔族和汉族溃疡性结肠炎危险因素的分析

背景:溃疡性结肠炎(UC)的发病在不同地区和民族之间存在差异,其发病率逐年增高,但发病原因至今仍不十分明确。目的:探讨新疆地区维吾尔族和汉族UC发病可能的危险因素。方法:纳入经结肠镜检查和病理活检确诊的93例初发型UC患者,其中维吾尔族患者46例,汉族患者47例,同时选择匹配的健康人作为对照。行问卷调查,对可能与UC发病相关的11个变量行单因素分析,差异有统计学意义的变量进一步行多因素条件logistic回归分析。结果:单因素分析显示:油腻饮食、阑尾切除、肠道感染、精神紧张、牛奶摄入与维吾尔族人群UC的发病相关(P<0.05);而吸烟、辛辣饮食、阑尾切除、肠道感染、精神紧张、牛奶摄入与汉族人群UC的发病相关(P<0.05)。多因素条件logistic回归分析显示:油腻饮食(OR=1.970,95%CI:1.412～2.785,P=0.000)、偶尔和经常牛奶摄入(OR=3.219,95%CI:1.190～8.567,P=0.005;OR=2.375,95%CI:1.024～6.649,P=0.004)可能是维吾尔族人群UC发病的危险因素;精神紧张(OR=1.975,95%CI:1.032～3.469,P=0.025)、经常牛奶摄入(OR=4.291,95%CI:1.418～11.913,P=0.012)可能是汉族人群UC发病的危险因素,而吸烟可能是保护因素(OR=0.076,95%CI:0.015～0.527,P=0.004)。结论:新疆地区维吾尔族和汉族UC的发病危险因素可能存在差异,对于维吾尔族人群,油腻饮食、牛奶摄入可能是UC发病的危险因素;而精神紧张、经常牛奶摄入可能是汉族人群UC发病的危险因素,吸烟可能是保护因素。     

Association of CTLA-4 gene microsatellite polymorphism with ulcerative colitis in Chinese patients

Ulcerative colitis (UC) is characterized by chronic intestinal inflammation as a result of an exaggerated T cell response. Cytotoxic T lymphocyte associated antigen-4 (CTLA-4), expressed mainly in activated T cells, inhibits T cell activation and proliferation by combining B7 through competing CD28 and maintains immune homeostasis. Polymorphisms of the CTLA-4 gene are known to be associated with several autoimmune diseases. The aim of this study was to investigate the association between the CTLA-4 gene microsatellite polymorphism and UC in Chinese patients. Unrelated 100 Chinese patients with UC and 140 healthy controls were studied. The (AT) repeats in the 3' untranslated region of exon 4 of the CTLA-4 gene were amplified by allele-specific polymerase chain reaction (PCR). The amplified products were electrophoresed on a 12% polyacrylamide gel, followed by silver staining. Twenty alleles were found in Chinese patients and healthy controls. The 122-bp allele was increased in UC compared with healthy controls (9.5% vs 0.7%, P = 0.0001/Pc = 0.002, OR = 14.591, 95%CI 3.357-63.420). The frequency of the longer alleles (>or=118 bp) of UC was higher than that in healthy controls (26% vs 4%, P = 0.0001/Pc = 0.0002, OR = 7.644, 95%CI 3.950-14.792), but was not associated with location and severity of the disease. Furthermore, the longer alleles were not associated with haplotypes of C-318T/A+49G of the CTLA-4 gene in Chinese patients with UC. The longer alleles of the CTLA-4 gene microsatellite polymorphism were strongly associated with UC in Chinese patients.     

Association of MHC class I related gene B (MICB) to celiac disease

BACKGROUND AND AIMS: Celiac disease (CD) is an enteropathic disorder characterized by strong association with HLA-DQ2. Our aim was to investigate whether MICB, a gene located in the MHC class I region, may contribute to CD susceptibility. PATIENTS AND METHODS: Total of 133 CD patients, previously reported to be associated with MICA-A5.1, and 116 controls were initially analyzed. Twenty-eight additional DQ2-negative CD patients were also studied. MICB was typed by PCR using sequence-specific primers. HLA-B, -DRB1, -DQA1, -DQB1, and MICA were also typed. RESULTS: The allele MICB0106 was strongly associated with CD (pc < 0.000001, odds ratio (OR) = 5.6, 95% confidence interval (CI) = 3.1-10.1) and it was overrepresented in atypical patients compared with typical ones (pc = 0.04, OR = 2.9, CI = 1.4-6.1). MICB0106 was part of DR3-DQ2 haplotype (B8-MICA-A5.1-MICB0106-DR3-DQ2), and consequently a strong linkage disequilibrium between MICB0106 with DQ2 (lambdas = 1) and MICA-A5.1 (lambdas = 0.55) was found. To analyze whether the association of MICB is independent of this haplotype, its association was also studied in DQ2-negative patients (n = 46). DQ8 (28%vs 9%, p = 0.0085, pc = NS) and MICB0104 (52%vs 30%, p = 0.01, pc = NS) were increased in DQ2-negative patients. MICA-A5.1 was significantly increased in atypical patients (p(c)= 0.001, OR = 6.4, CI = 2.2-18.4), and this association was independent of DQ2 and DQ8 (pc = 0.02, OR = 2.6, CI = 1.1-6.1). CONCLUSIONS: The expression of MIC genes on enterocytes under stressful conditions and their function as ligands of intraepithelial gammadelta and CD8 T cells, together with the data presented here suggest a potential role of MIC genes in the pathogenesis of CD.     

Vitamin D receptor gene polymorphism and ulcerative colitis susceptibility in Han Chinese

OBJECTIVE: Specific polymorphisms in the vitamin D receptor (VDR) gene have been associated with genetic susceptibility to inflammatory bowel disease (IBD) in different ethnic populations. METHODS: A total of 218 ulcerative colitis (UC) patients and 251 healthy controls were genotyped for VDR gene polymorphisms using PCR‐restriction fragment length polymorphism (PCR‐RFLP) assay. VDR gene polymorphisms (Apa I, Taq I, Bsm I and Fok I) were analyzed for both genotypic and phenotypic susceptibilities. RESULTS: Among the four examined VDR gene polymorphisms, the Bsm I polymorphism showed a slightly higher distribution in our study population than that in the previous studies. We also found that the increased frequency of the Bb genotype of the Bsm I VDR gene polymorphism was associated with UC in Han Chinese, as compared with healthy controls (28.4% vs. 18.7%, χ² = 6.044, P = 0.014, OR = 1.739, 95% CI = 1.122–2.697). Moreover, Bsm I polymorphic allele (B) frequency was significantly increased in the UC cases, as compared to the healthy controls (14.7% vs. 7.8% χ² = 6.222, P = 0.013; OR = 1.670, 95% CI = 1.113–2.506). In contrast, the other three VDR gene polymorphisms (Apa I, Taq I and Fok I) were not associated with UC susceptibility in the Han Chinese cohort. In addition, none of these four VDR polymorphisms had statistical association with clinicopathological parameters of these UC patients. CONCLUSION: This study demonstrated a probable association of the Bsm I polymorphism of the VDR gene with ulcerative colitis susceptibility in Han Chinese.     

MHC class I chain-related gene B (MICB) is associated with rheumatoid arthritis susceptibility

OBJECTIVES: Several recent studies have shown that the MHC class III region, located telomeric to HLA-DRB1, contains an additional genetic factor that predisposes to rheumatoid arthritis (RA). In this study, we investigate whether inhibitor of kappaB-like (IkappaBL), MICB or MICA located in the MHC class III region are the second susceptibility gene associated with RA. METHODS: A total of 154 healthy controls and 140 RA patients were genotyped for HLA-DRB1, MICA, MICB and the polymorphism -62 of the IkappaBL gene. RESULTS: A significant increase of HLA-DRB1 shared epitope (SE) alleles was detected in RA patients (61.4 vs 43.5%, P(c) = 0.01, OR = 2.1, 95% CI = 1.3-3.3). Among SE alleles, the HLA-DRB1*0401 (13.5 vs 5.1%, P(c) = 0.04, OR = 3.2, 95% CI = 1.3-8.1) and HLA-DRB1*0404 (6.4 vs 1.2%, P = 0.02, P(c) = NS) showed the most significantly association with RA. No increase of risk was associated with HLA-DRB1*01. Remarkably, the allele MICB*004 was also significantly associated with RA susceptibility (40.7 vs 23.3%, P(c) = 0.01, OR = 2.2, 95% CI = 1.3-3.7). MICB*004 was in linkage disequilibrium with HLA-DRB1*0404 (lambda(s) = 0.33) and HLA-DRB1*0405 (lambda(s) = 0.34). However, MICB*004 was also increased in HLA-DRB1 SE negative patients (37 vs 21.5%, P = 0.04). No significant association between IkappaBL and MICA with RA was found. CONCLUSIONS: MICB*004 allele was associated with RA susceptibility. This allele was in linkage disequilibrium with HLA-DRB1*0404 and DRB1*0405. The association of MICB with RA susceptibility and the functional role of MIC genes in the pathogenesis of RA converts MICB into a candidate to be an additional MHC gene associated with RA susceptibility.     

细胞毒T淋巴细胞相关抗原4基因多态性与汉族溃疡性结肠炎患者的相关性研究

目的　研究细胞毒T淋巴细胞相关抗原4(CTLA- 4)基因外显子1的49位点A/G和启动子- 318位点C/T多态性与溃疡性结肠炎(UC)的相关性。方法　采用序列特异性引物聚合酶链反应(PCR -SSP)方法,检测82例中国湖北汉族溃疡性结肠炎患者(UC)以及204 例健康对照者CTLA- 4 基因外显子1的49位点A/G和启动子-318位点C/T的基因型和单倍型。结果　UC患者CTLA -4 A+49G和C- 318T基因型与正常对照组间差异无统计学意义(P>0.05),且与性别无关。在单倍型分析中,UC患者CTLA -4单倍型2,3(C-318 G49/T-318 A49)显著低于正常人群(26%比41%,P<0.05,OR=0.4918,95%CI:0.2784~0.8688)。结论　UC患者CTLA- 4 基因A+49G和C -318T单倍型2,3 与UC呈负相关。     

DLG5 R30Q is not associated with IBD in Hungarian IBD patients but predicts clinical response to steroids in Crohn's disease

BACKGROUND: Recent data suggest that haplotypic variants of the DLG5 gene on 10q23 are associated with susceptibility to inflammatory bowel disease (IBD) in Germany. In view of the geographical differences in frequency of genetic markers and the absence of data in Central European patients, our aim was to determine the DLG5 R30Q variant in Hungarian IBD patients. MATERIALS AND METHODS: We investigated 773 unrelated IBD patients (age 38.1 +/- 10.3 years; duration, 8.8 +/- 7.5 years; Crohn's disease [CD]: 639; male/female, 309/330; duration, 8.4 +/- 7.1 years; ulcerative colitis [UC]: 134; male/female, 63/71; duration, 10.6 +/- 8.9 years) and 150 healthy subjects. DLG5 R30Q and TLR4 D299G variants were tested by polymerase chain reaction/restriction fragment length polymorphism. DNA was screened for NOD2/CARD15 mutations by denaturing high-performance liquid chromatography. Detailed clinical phenotype was determined by reviewing the medical charts. RESULTS: The frequency of the R30Q variant allele was not significantly different in IBD (22.0%), CD (20.8%), and UC (27.6%) patients compared with healthy control subjects (28.0%). In CD, the 113A variant allele was associated with steroid resistance (16.3% vs noncarriers, 7.6%; odds ratio [OR], 2.4; 95% CI 1.3-4.5; P = 0.013). In a logistic regression model carriage of DLG5 R30Q, perianal involvement and frequent relapses were independently associated with steroid resistance. No phenotype-genotype associations were found in UC patients, although a trend toward more extensive disease was observed in carriers of the variant allele (OR = 2.1; 95% CI 0.95-4.4; P = 0.07). CONCLUSIONS: The present data strongly contrast previous data from Germany. DLG5 113A is not associated with disease susceptibility, but there was a tendency for this allele to confer resistance to steroids. Further studies are required to evaluate the significance of DLG5 in other populations from geographically diverse regions.