LMP2与LMP7基因多态性及强直性脊柱炎并发虹睫炎易感性关？…

目的 研究ＬＭＰ基因多态性与强直性脊柱炎并发虹睫炎发病的关系。方法 应用ＰＣＲ对正常人和病人进行ＨＬＡ－Ｂ２７检测以及ＬＭＰ２和ＬＭＰ７扩增。ＣｆｏＩ进行限制性酶切图谱分析。结果 强直性脊柱炎有虹睫炎（ＡＳ＋ＡＡＵ）病史以及单纯虹睫炎（ＡＡＵ）患者ＬＭＰ２基因ＢＢ纯合型较正常人以及强直性脊柱炎（ＡＳ）患者明显增高（Ｐ〈０．０５）。ＡＳ＋ＡＡＵ患者ＬＭＰ２基因ＢＢ纯合型较正常人以及强直性脊柱炎（ＡＳ     

HLA-DQB1 基因与中国湖北汉族人 SLE 及其自身抗体的相关性研究

目的：探讨ＨＬＡＤＱＢ１等位基因与系统性红斑狼疮（ＳＬＥ）及其自身抗体的相关性。方法：采用ＰＣＲ／ＳＳＰ技术对５２例中国湖北地区汉族ＳＬＥ患者及１４３例正常对照者进行了ＨＬＡＤＱＢ１基因分型，并采用免疫印迹技术检测患者血清中自身抗体。结果：ＳＬＥ患者ＤＱＢ１０６０８（９６２％，χ２＝１０５１，Ｐ＜０００５）基因频率显著升高，ＤＱＢ１０３０２（５７７％，ＲＲ＝０２６Ｐ＜００５，ＰＦ＝０１４）和ＤＱＢ１０５０１（１９２％，ＲＲ＝０１１，Ｐ＜００１，ＰＦ＝０１３）基因频率显著降低，与正常对照组比较，ＤＱＢ１０６０８在伴抗Ｓｍ（１０３４％，Ｐ＜０００５）、抗ＲＮＰ（１１５４％，Ｐ＜０００５）、抗ｄｓＤＮＡ（２２２２％，Ｐ＜０００５）抗体阳性的ＳＬＥ患者中频率显著升高。结论：ＤＱＢ１０６０８与ＳＬＥ关联，并分别与抗Ｓｍ、抗ＲＮＰ、抗ｄｓＤＮＡ抗体的产生有相关性。而ＤＱＢ１０３０２、ＤＱＢ１０５０１等位基因对ＳＬＥ可能具有保护性。     

糖尿病酮症酸中毒并肝损害临床分析

目的探讨导致糖尿病酮症（ＤＫ）及酮症酸中毒（ＤＫＡ）患者肝损害的相关因素．方法ＤＫ或ＤＫＡ患者９９例,其中ＡＬＴ及ＡＳＴ均异常升高１１例（Ａ组）,单项ＡＬＴ异常升高１３例（Ｂ组）,肝功能正常７５例（Ｃ组）,对以上各组患者的血二氧化碳结合力（ＣＯ２ＣＰ）、尿素氮（ＢＵＮ）、血糖（ＢＧ）和血浆渗透压（ＯＳＭ）进行了统计分析．结果Ａ,Ｂ两组患者的ＣＯ２ＣＰ明显低于Ｃ组（Ｐ＜００１,ｔ＝６３３和ｔ＝６４３）,而ＢＵＮ则明显升高（Ｐ＜００１,ｔ＝３６１,ＡｖｓＣ;Ｐ＜００１,ｔ＝４３５,ＢｖｓＣ）,Ａ组的ＢＧ（Ｐ＜００５,ｔ＝２８４）和血浆ＯＳＭ（Ｐ＜００５,ｔ＝３１０）水平也显著高于Ｃ组,而Ｂ组患者的ＢＧ及血浆ＯＳＭ与Ｃ组比较无差异;与Ｂ组相比,Ａ组患者的ＣＯ２ＣＰ明显降低（Ｐ＜００２,ｔ＝２７１）,ＢＧ（Ｐ＜００５,ｔ＝２８９）和血浆ＯＳＭ（Ｐ＜００５,ｔ＝２３６）明显升高．此外,Ⅰ型糖尿病患者血清转氨酶异常升高的发生率明显高于Ⅱ型糖尿病患者（Ｐ＜００５,χ２＝４３８）．结论酸中毒和脱水是导致糖尿病酮症及酮症酸中毒患者肝损害的重要因素,酸中毒及脱水程度与肝损害程度相关．     

慢性胃炎血清sIL─2R及RBC免疫功能的研究

目的研究慢性胃炎患者血清ｓＩＬ＿２Ｒ及ＲＢＣ免疫功能的变化。方法内镜及病理检查确诊的慢性胃炎５１例和４０例正常对照组作血清ｓＩＬ＿２Ｒ（双抗体夹心ＥＬＩＳＡ法）及ＲＢＣＣ３ｂ受体花环率、ＲＢＣ免疫复合物花环率（酵母菌花环试验）测定。结果慢性胃炎患者血清ｓＩＬ＿２Ｒ水平（２７５０±２３１１ＫＵ／Ｌ）与正常对照组（１９０６±７９３ＫＵ／Ｌ）相比增高，ＲＢＣ免疫功能降低；上述改变在慢性萎缩性胃炎及合并Ｈｐ感染者更明显（Ｐ＜００１）。血清ｓＩＬ＿２Ｒ与ＲＢＣＣ３ｂＲＲ呈负相关（ｒ＝－０５７，Ｐ＜００１）；与ＲＢＣＩＣＲ呈正相关（ｒ＝０７２，Ｐ＜００１）。结论慢性胃炎患者有免疫功能紊乱，血清ｓＩＬ＿２Ｒ及ＲＢＣ免疫功能低下，可能与慢性胃炎的发生发展有关     

解偶联蛋白2基因Ala55Val变异与中国人2型糖尿病患者葡萄糖兴奋后胰岛素分泌功能的关系

目的　解偶联蛋白２（ Ｕ Ｃ Ｐ２） 基因定位于人类１１ｑ 染色体区,该区域与高胰岛素血症及肥胖相关连。本研究拟探讨 Ｕ Ｃ Ｐ２ 基因 Ａｌａ５５ Ｖａｌ（ Ａ／ Ｖ５５） 变异与中国人２ 型糖尿病患者胰岛素分泌／ 敏感性的关系。方法　３５９ 例无亲缘关系的中国人（ 据９７ 年 Ａ Ｄ Ａ 标准分为：糖耐量正常者１９３ 例,２ 型糖尿病１６６ 例） 及６６ 例白种人用 Ｐ Ｃ Ｒ Ｒ Ｆ Ｌ Ｐ 检测 Ｕ Ｃ Ｐ２ 基因 Ａ／ Ｖ５５ 变异。结果　中国人（ Ａ Ａ０ ．３１ , Ａ Ｖ０ ．５１ 及 Ｖ Ｖ０ ．１８） 与白种人（ Ａ Ａ０ ．３２ , Ａ Ｖ０ ．５６ 及 Ｖ Ｖ０ ．１２） Ｕ Ｃ Ｐ２ 基因 Ａ／ Ｖ５５ 变异的基因型频率分布无显著差异（ Ｐ＝ ０ ．６１５） ,且该基因变异与中国人２ 型糖尿病发病无相关性（ Ｐ＝ ０ ．５５８） 。在１６６ 例２ 型糖尿病患者中, Ｕ Ｃ Ｐ２ 基因 Ａ／ Ｖ５５ 变异与 糖负荷３ 小时 胰岛素总值（ Ｓ Ｕ Ｍ）（ Ｐ＝０ ．０１０８） ,胰岛素曲线下面积（ Ａ Ｕ Ｃ）（ Ｐ＝ ０ ．０１４９） 以及 Ｈ Ｏ Ｍ Ａβ细胞功能（ Ｐ＝ ０ ．０１７４） 相关。且糖负荷３ 小时 Ｃ 肽总值及 Ｃ 肽曲线下面积变化亦与胰岛素有相同趋势。结论　 Ｕ Ｃ Ｐ     

中国汉族系统性红斑狼疮某些易感基因的研究

为了探索我国北方汉族人群人类白细胞抗原－ＤＲ（ＨＬＡ－ＤＲ）及肿瘤坏死因子Ｂ（ＴＮＦＢ）等位基因多态性与系统性红斑狼疮（ＳＬＥ）的易感性关系，对１０６例健康人和４５例ＳＬＥ患者的ＨＬＡ－ＤＲ和对８０例健康人及４５例ＳＬＥ患者的ＴＮＦＢ等位基因，采用多聚酶链反应－限制性酶切片段长度多态性（ＰＣＲ－ＲＦＬＰ）法进行分析。结果显示：ＳＬＥ患者中频率显著升高的等位基因有ＤＲ２［Ｐ＜０．０５，相对危险性（ＲＲ）＝１．５６］及ＤＲ３（Ｐ＜０．０１，ＲＲ＝２．６９）。而ＤＲ５和对照相比呈相反结果（Ｐ＜０．０５，ＲＲ＝０．４３）。ＳＬＥ患者ＴＮＦＢ＊２等位基因频率显著增高（Ｐ＜０．０５，ＲＲ＝１．８４）。提示ＤＲ２、ＤＲ３、ＴＮＦＢ＊２可能是易感等位基因或易感等位基因标记，而ＤＲ５是一拮抗等位基因或拮抗等位基因标记。并研究了ＨＬＡ－ＤＲ、ＴＮＦＢ等位基因与患者血浆中Ｓ蛋白和补体５ｂ－９结合物的复合物（ＳＣ５ｂ－９）的水平和多种自身抗体及狼疮肾炎、狼疮肺炎、狼疮脑病等狼疮并发症之间的相关性，发现ＨＬＡ－ＤＲ２基因与狼疮肾炎的发生存在正相关（Ｐ＜０．０５，ＲＲ＝１．３２）。     

非胰岛素依赖型糖尿病患者血管紧张素转换酶与慢性并发症的关系

目的探讨非胰岛素依赖型糖尿病（ＮＩＤＤＭ）患者血清血管紧张素转换酶（ＳＡＣＥ）水平及其与各种慢性并发症的关系。方法６７例ＮＩＤＤＭ患者用紫外法测定ＳＡＣＥ水平。结果ＮＩＤＤＭ全组ＳＡＣＥ为（３３９±１２４）Ｕ／Ｌ，明显高于正常人［（２８．１±５．７）Ｕ／Ｌ］，Ｐ＞００１。其中超出正常范围（３９５Ｕ／Ｌ）者１８例，占２７％；糖尿病肾病（ＤＮ）者（３０例）ＳＡＣＥ更高［（４２６±１０．６）Ｕ／Ｌ］，而无ＤＮ者［３７例，（２６９±５．７）Ｕ／Ｌ］与正常人无异。结论ＮＩＤＤＭ患者ＳＡＣＥ升高与病程、ＤＮ、视网膜病变（ＤＲ）、神经病变、心血管病变等慢性并发症有关。为临床应用ＡＣＥ抑制剂防治糖尿病慢性并发症提供部分依据。     

汉族人群抗原处理相关转运体(TAP)基因多态性及与类风湿关节炎的相关性

目的探讨汉族人群抗原处理相关转运体（ＴＡＰ）基因多态性及与类风湿关节炎（ＲＡ）的相关性。方法用ＰＣＲＡＲＭＳ,ＲＦＬＰ,ＳＳＯＰ检测ＲＡ患者７８例及健康献血者７３名ＴＡＰ１３３３位和６３７位,ＴＡＰ２３７９,５６５,６５１,６８７位氨基酸等位基因多态性。结果汉族健康人ＴＡＰ１３３３位的６３７位等位基因基因型分别以Ｉ和Ｄ为主,表现型主要为Ⅱ和ＤＤ,有１Ａ１Ｄ４个亚型,以１Ａ和１Ｂ为主,有６种表型,ＴＡＰ２３７９,５６５,６５１,６８７位基因型分别以ＶＡＲＴＳ为主,表型以ＶＶＡＴＲＲＡＴＳＳ为主,有２Ａ２Ｇ７个亚型,以２Ａ和２Ｂ为主,有９种表型。ＲＡ患者ＴＡＰ２５６５ＴＴ和６６５ＡＡ及ＴＡＰ２Ｄ频率升高,并可使ＤＲ４阳性者患ＲＡ的相对危险性增加８２６倍。２Ｄ及ＤＲ４阳性ＲＡ患者的ＲＦ滴度显著高于ＴＡＰ２Ｄ阴性而ＤＲ４阳性的ＲＡ患者及前者的病程较长。结论汉族人群ＴＡＰ基因多态性有其基本特点。ＴＡＰ２Ｄ可使ＤＲ４阳性者患ＲＡ的相对危险性增加并可能影响其临床表现。     

脑梗塞患者载脂蛋白B基因3′端小卫星区的多态性研究

采用聚合酶链反应（ＰＣＲ）对８４ 例动脉粥样硬化性脑梗塞（ＡＣＩ）患者（ＡＣＩ组）的载脂蛋白Ｂ（ａｐｏＢ）基因３′端小卫星区（ＭＳＲ）的ＤＮＡ多态性进行研究,并与１０７ 例正常人（对照组）进行比较。结果两组ａｐｏＢ基因３′端等位基因分布频率均以ＭＳＲ３７ 和ＭＳＲ３９ 最高,ＡＣＩ组分别为０．４８、０．１９,对照组分别为０．５０、０．１７,且ＡＣＩ组的大拷贝等位基因（ＭＳＲＢ）分布频率增高。组内及组间分析显示,ＭＳＲＢ与血清ａｐｏＢ以及ＬＤＬ－ｃｈ 增高有关;３′端ＭＳＲ等位基因是已知ａｐｏＢ基因的有用标记;大片段ＭＳＲ等位基因与ＡＣＩ有相关性,支持不同拷贝数目的基因多态性可影响血脂水平代谢;位于ａｐｏＢ３′端的ＭＳＲ等位基因的多态性,可能是动脉粥样硬化多源性病因的一部分,其可能涉及病理过程中胶原暴露及内皮损伤,并共同参与ＡＣＩ的发病。     

小檗碱治疗分泌性腹泻的实验研究

目的探讨小檗碱（Ｂｅｒ）对分泌性腹泻豚鼠离体回肠电解质转运的影响．方法利用霍乱毒素（ＣｈＴ）制成分泌性腹泻模型．通过ＵｓｓｉｎｇＣｈａｎｂｅｒ技术测定豚鼠离体回肠膜电位差（ＰＤ）、膜短路电流（ＳＣＣ）和膜电阻（Ｒ）．结果①分泌性腹泻时，豚鼠离体回肠的ＰＤ和ＳＣＣ均显著高于正常对照组（ｔ＝３５２０，ｔ＝３１８２，Ｐ＜００１）；②加于粘膜侧（Ｍ）溶液中１０ｍｍｏｌ／Ｌ的Ｂｅｒ和加于浆膜侧（Ｓ）溶液中０１ｍｍｏｌ／Ｌ及０５ｍｍｏｌ／Ｌ的Ｂｅｒ均可降低ＰＤ和ＳＣＣ（ｔ＝１４２７，１６８２，ｔ＝１１６５，１２８５，Ｐ＜００１），但不改变Ｒ（ｔ＝０４３，１８７，Ｐ＞００５），而加于Ｓ侧溶液中１０ｍｍｏｌ／Ｌ的Ｂｅｒ不仅可降低ＰＤ和ＳＣＣ（ｔ＝１９０２，ｔ＝１５４５，Ｐ＜００１），还可降低Ｒ（ｔ＝２１５，Ｐ＜００５）．结论Ｂｅｒ可抑制由ＣｈＴ所致的电解质分泌亢进     

Polymorphism of the LMP2 gene and disease phenotype in ankylosing spondylitis: No association with disease severity

Summary Although a number of reports have now described an association between polymorphism of the LMP2 gene and disease phenotype in HLA-B27 positive individuals with ankylosing spondylitis (AS), some describe associations with acute anterior uveitis, others with juvenile onset disease, and one report provides no association. A recent study describes yet a further association with disease severity in patients with juvenile rheumatoid arthritis. We therefore hypothesized that the discrepant findings in adult disease may be a reflection of an underlying association with disease severity. Our study population consisted of 100 HLA-B27 positive Caucasians with AS of ten or more years duration. Clinical assessment of disease severity was based on a metrology index scoring five measurements, the modified health assessment questionnaire for the spondyloarthropathies, and a disease activity index consisting of a visual analog scale to score the amount of pain, stiffness and fatigue. LMP2 genotypes were assigned following polymerase chain reaction amplification from genomic DNA and restriction enzyme digestion with CfoI. Despite confirmation of a significantly higher prevalence of the LMP2 BB genotype in AAU positive (66.0%) versus AAU negative (45.2%) patients (P<0.05), we observed no association between LMP2 genotypes and any of the indices of disease severity. Furthermore, although a significant association was noted between the presence of peripheral synovitis and the functional index score (P<0.05), a history of AAU was not associated with more severe disease. Our data is thus internally consistent in demonstrating no association between LMP2 genotypes and either disease severity or peripheral arthritis, and supports the notion that polymorphism of LMP2 primarily influences the development of AAU and not some other phenotype of AS.     

LMP2 polymorphism is associated with extraspinal disease in HLA-B27 negative Caucasian and Mexican Mestizo patients with ankylosing spondylitis

OBJECTIVE: To determine the effects of HLA Class II genes, particularly LMP2 and previously implicated Class I genes, on susceptibility and disease expression in HLA-B27 negative ankylosing spondylitis (AS). METHODS: Patients included 41 HLA-B27 negative Caucasians from a total AS population of 546 and 17 HLA-B27 negative Mexican Mestizo. Controls included 4352 random HLA-B27 negative Caucasians. LMP2 genotype assignments were made on all patients and 282 random Caucasian controls by polymerase chain reaction-restriction fragment length polymorphism with the Cfo I restriction enzyme while HLA typing was performed on patients and controls using microcytotoxicity assays for Class I, and sequence specific probe-PCR for HLA-B60, B39, B38, and DR. RESULTS: The LMP2BB genotype was significantly decreased in Caucasian AS patients without extraspinal (ES) disease (25%) compared to AS patients with ES (64.7%) (p = 0.01) and random Caucasian controls (53.9%) (p = 0.007), even when those with colitis and psoriasis were excluded from analysis (ES+ 55.6% versus ES- 22.2%). This finding remained significant after stratification by HLA-DR. Similar trends were noted in the Mexican population. A potential role for HLA-DR8 and DR2 in susceptibility to disease was observed in Caucasian patients, although this observation requires confirmation. We could not confirm reported associations with HLA-B60 or B39. Peripheral arthritis was significantly more commonly observed in those who had had acute anterior uveitis (AAU) (75%) than in those who had not developed AAU (27.3%) (p = 0.04). CONCLUSION: HLA Class II encoded genes may have effects on disease susceptibility and/or phenotype in HLA-B27 negative individuals similar to those noted in HLA-B27 positive AS. Eccentric and axial phenotypes of disease may be immunogenetically determined.     

The LMP2 polymorphism is associated with susceptibility to acute anterior uveitis in HLA-B27 positive juvenile and adult Mexican subjects with ankylosing spondylitis

INTRODUCTION—An association between polymorphism of the HLA linked LMP2 locus and the development of acute anterior uveitis (AAU) has previously been described in B27 positive white subjects with ankylosing spondylitis (AS). This study evaluated LMP2 alleles in two HLA-B27 positive Mexican populations of patients with spondyloarthropathy known to have a different clinical spectrum of disease from white people.
PATIENTS AND METHODS—The study populations consisted of 90 AS patients from Guadalajara with predominantly adult onset disease and 80 AS patients from Mexico City with predominantly juvenile onset disease. LMP2-CfoI amplified fragment length polymorphisms were determined after polymerase chain reaction amplification and digestion with CfoI restriction enzyme.
RESULTS—There was an increased LMP2A allelic frequency in patients who had had AAU in both Guadalajara (31.8%) and Mexico City (33.3%) when compared with non-AAU patients (15.2% and 17.7% of Guadalajara and Mexico City populations, respectively). The odds ratio relating LMP2A allelic frequency and AAU for the combined population, stratified by age at onset of disease, was 2.51 (p=0.01). LMP2 alleles did not influence the age at onset of disease or the development of peripheral arthritis.
CONCLUSIONS—These data support the view that polymorphism at the LMP2 locus is associated with the development of AAU in B27 positive subjects with AS. The requirement for both the less common LMP2 allele and HLA-B27 is consistent with the low prevalence of AAU in Mexican patients with spondyloarthritis.

     

Polymorphism in the LMP2 gene influences susceptibility to extraspinal disease in HLA-B27 positive individuals with ankylosing spondylitis.

OBJECTIVE--To investigate the potential influence of the HLA-linked LMP2 gene on disease susceptibility in HLA-B27 individuals with ankylosing spondylitis (AS). METHODS--A polymorphic CfoI restriction enzyme site in the coding region of the LMP2 gene was evaluated in genomic DNA samples from 193 white and 49 Chinese B27 individuals with well documented AS, 97 of whom had had acute anterior uveitis (AAU) and 97 peripheral arthritis; 42 samples from normal, white, B27 positive blood donors in whom AS was excluded were also evaluated. RESULTS--Analysis of B27 white AS individuals with AAU, peripheral arthritis, or both, revealed significant differences in genotypic distribution of this bi-allelic locus compared with B27 AS patients without extraspinal manifestations (p < 0.005) or B27 controls (p < 0.01). Furthermore, homozygosity for one LMP2 gene allele was significantly more prevalent in AS patients with AAU (71.3%) (p < 0.01) or peripheral arthritis (68.3%) (p < 0.02) than in B27 controls (45.2%). A similar genotypic distribution was noted in B27 Chinese AS individuals with extraspinal manifestations compared with those with axial disease alone. CONCLUSIONS--These findings support the involvement of the HLA linked LMP2 gene in the expression of disease in B27 individuals and represent a novel finding in rheumatic disease.     

Polymorphism in the MHC-encoded LMP7 gene: association with JRA without functional significance for immunoproteasome assembly.

OBJECTIVE: To determine if a polymorphism in the immunoproteasome subunit LMP7 was associated with juvenile rheumatoid arthritis (JRA) and had functional significance. METHODS: The frequency of LMP7QQ+ vs QQ- (QK and KK genotypes) among 207 patients with JRA and 50 controls was determined. JRA subtypes were pauciarticular (53%), polyarticular (33%), and systemic (14%). Onset was before age 6 (early onset) in 60% of patients. The functional significance of the LMP7 polymorphism was determined by comparing incorporation of LMP7Q vs LMP7K into proteasomes. RESULTS: There was an increased frequency of LMP7QQ in patients vs controls (73 vs 56%; p = 0.016), mainly due to the pauciarticular and systemic JRA subtypes (p = 0.037), and more pronounced in early onset disease (77 vs 56%; p = 0.006). The association persisted with stratification for HLA-DR5(11) and -DPB 1 *0201 (p = 0.002 and 0.013). We found no difference in the relative incorporation of LMP7Q and LMP7K into proteasomes. CONCLUSIONS: These results support an association between LMP7QQ homozygosity and JRA, particularly early onset disease. The difference persists with stratification, at least for DR5(11) and DPB1*0201, suggesting that this effect is unlikely to be due to linkage disequilibrium with HLA alleles known to be associated with early onset pauciarticular JRA. Importantly, as there does not appear to be functional significance associated with the LMP7 polymorphism, this may be a marker for another as yet unidentified susceptibility locus.     

Genetic markers for acute anterior uveitis

One hundred and sixty-nine patients, 82 with acute anterior uveitis (AAU) only, 48 with AAU and ankylosing spondylitis (AS), and 39 with AS only were studied. The HLA antigen A2 was present in 44/82 AAU only, 31/48 AAU + AS, and 23/39 AS only. Where haplotype analysis was possible by virtue of family studies, A2 B27 was present in 7/16 AAU only, 9/15 AAU and AS and 14/29 AS only. These figures do not differ significantly from the expected values of control populations. Alpha-1-antitrypsin (alpha-1-AT) phenotypes were obtained on 30/82 AAU only, 29/48 AAU + AS, and 27/39 AS only patients. The MZ phenotype appeared in 8/86 patients tested; 4/30 with AAU only and 4/29 AAU + AS patients. This is higher than the expected value for control populations. Therefore, MZ alpha-1-AT phenotype but not HLA-A2 appears increased in patients with AAU.     

LMP2/LMP7 gene variant: a risk factor for intestinal Mycobacterium tuberculosis infection in the Chinese population

Background and Aims: Low molecular mass protein‐2 (LMP2) and low molecular mass protein‐7 (LMP7) genes play a critical role in foreign antigen processing on the major histocompatibility complex‐I CD8⁺ cytotoxic T‐lymphocyte pathway. This study was designed to investigate whether the sequence variants in the LMP2/LMP7 coding region were associated with intestinal Mycobacterium tuberculosis (M. tuberculosis) infection or with the co‐infection of pulmonary tuberculosis. Methods: A total of 168 patients with intestinal tuberculosis and 235 normal controls were recruited for this study. Two polymorphisms of LMP2 (Arg60–His) and LMP7 (Gln145–Lys) were identified by polymerase chain reaction–restriction fragment length polymorphism method. The associations of the LMP2/LMP7 genotype and haplotype with intestinal M. tuberculosis infection were assessed by using logistic regression analysis. Results: The results revealed that LMP7 position codon 145 Lys/Lys and Gln/Lys alleles in the coding region were associated with the infection of intestinal M. tuberculosis (P = 0.003, odds ratio [OR] = 3.86 and P < 0.001, OR = 2.28, respectively). Meanwhile, the Arg–Lys and Cys–Lys haplotypes exhibited significant relation to the intestinal M. tuberculosis infection (P = 0.006, OR = 1.87; P = 0.021, OR = 1.83, respectively). No significant associations were observed for any of the single‐nucleotide polymorphism genotypes or haplotypes with the co‐infection of pulmonary tuberculosis (P > 0.05). Conclusions: The results indicated that the genetic variant within the LMP2/LMP7 gene would increase the risk of intestinal M. tuberculosis infection.     

LMP2/LMP7基因编码区多态性及单倍体型与胃癌易感无相关性

目的:探讨中国汉族人群中肿瘤抗原递呈的限速基因LMP2/LMP7单核苷酸多态性与胃癌的遗传易感性关联.方法:提取145例胃癌患者及152例健康献血员外周血基因组DNA,用PCR-RFLP方法检测两组人群中LMP2-codon60/LMP7-codon145两个多态性位点的基因型;并采用PHASE1.0软件构建这两个多态性位点的个体单倍体型,以非条件Logistic回归校正混杂因素,并进行多态性与胃癌患者风险关联的统计学分析.结果:PCR-RFLP检测结果显示:LMP2-codon60与LMP7-codon145处的多态性在中国人群中普遍存在,LMP2/LMP7多态性位点的各自的等位基因频率分布符合Hardy-Weinberg平衡定律;最后的统计分析表明:在145例胃癌患者与152例健康对照人群中LMP2/LMP7两个多态性位点的基因型频率、以及所构建的4个单倍体型频率均没有统计学差异(P值均大于0.05).结论:在中国汉族人群中,LMP2/LMP7基因编码区两个位点的多态性以及单倍体型与胃癌易感无相关性.     

Association of the large multifunctional proteasome (LMP2) gene with Graves' disease is a result of linkage disequilibrium with the HLA haplotype DRB1*0304-DQB1*02-DQA1*0501

OBJECTIVE: The large multifunctional proteasome (LMP) molecules are over expressed in thyrocytes, the target cells of Graves' disease, and the LMP genes are found within the MHC class II region. The LMP genes may therefore play a role in susceptibility to Graves' disease. The aim of this this study was to determine whether polymorphisms of the LMP genes, LMP 2 and LMP 7 are in linkage disequilibrium with Graves' disease. DESIGN: Target DNA was amplified using the polymerase chain reaction. The distribution of an Arg-His polymorphism in the LMP 2 gene and a G/T polymorphism in the LMP 7 gene, both of which lead to the presence of an HhaI restriction site, were investigated in a population based case control and family based study in patients with Graves' disease. PATIENTS: We obtained DNA from 306 patients with Graves' disease and 364 control subjects for the population based case-control study. In an independent family based study, DNA was obtained from 129 families including both parents, an affected sibling with Graves' disease and an unaffected sibling. All families, patients and control subjects were white caucasians. MEASUREMENTS: Frequencies of the alleles and genotypes of the LMP 2 and LMP 7 genes were compared between patients and control subjects using the chi2 test. Transmission of alleles from heterozygous parents to affected and unaffected offspring was assessed using the transmission disequilibrium test (TDT). RESULTS: In the case control study, no difference in allele or genotype frequency was seen between patients and control subjects at the LMP7 locus. At the LMP2 locus the R allele and the RH genotype were increased in subjects with Graves' disease when compared with control subjects (R allele: 36.3% vs. 29.5%, pc = 0. 0164; RH genotype: 56.5% vs. 45%, pc = 0.0102). However, the R allele was in linkage disequilibrium with the associated HLA DRB1*0304-DQB1*02-DQA1*0501 haplotype, delta = 0.102. Within the family based study, no preferential allelic transmission was seen from heterozygote parents to offspring at either loci. CONCLUSION: These results show that association of the LMP 2 locus with Graves' disease is due to linkage disequilibrium with the associated HLA haplotype DRB1*0304-DQB1*02-DQA1*0501.     

Hla–dr8 and acute anterior uveitis in ankylosing spondylitis

Objective. To identify possible factors in the development of acute anterior uveitis (AUU) in patients with ankylosing spondylitis (AS). Methods. We investigated HLA antigens serologically, and HLA–DRB1^*08 alleles by polymerase chain reaction–restriction fragment length polymorphism, in 42 Japanese AS patients with and without AAU. Results. Thirty-six of the AS patients (85.7%) had HLA–B27. Thirteen (65%) of the 20 patients with AAU had HLA–DR8, whereas only 1 (4.5%) of the 22 patients without AAU had DR8. The difference was statistically significant (P_corr < 0.001). Conclusion. Our data suggest that HLA–B27 is strongly associated with AS in Japanese patients and that HLA–DR8 is important for the development of AAU in Japanese patients with AS.