强直性脊柱炎与IL-23R基因多态性关联的Meta分析

探讨IL-23R基因多态性与中国人群强直性脊柱炎的相关性。系统检索PubMed、FMJS、CNKI及万方数据库有关IL-23R基因多态性与强直性脊柱炎相关的病例对照研究,应用ReveMan 5.2软件进行Meta分析。本研究共纳入IL-23R基因多态性与强直性脊柱炎相关文献9篇。Meta分析结果显示:IL-23Rrs1004819(OR=1.02,95%CI:0.90~1.14)、rs11209032(OR=0.91,95%CI:0.74~1.11)、rs1343151(OR=0.80,95%CI:0.59~1.08)和rs10889677(OR=0.95,95%CI:0.83~1.09)与强直性脊柱炎无显著关联,rs10489629(OR=0.78,95%CI:0.64~0.95)是强直性脊柱炎的保护性因素。可见部分IL-23R基因多态性与中国人群AS易感性无关联,需要进一步探索与中国人群AS易感性相关的其他基因位点。     

中国山东沿海地区汉族男性人群白介素-23受体基因多态性与痛风的易感性研究

目的探讨中国山东省沿海地区汉族男性群体的白细胞介素23受体（IL-23R）基因rs7517847位点G／T的多态性是否与痛风的易感性有关。方法选取202例痛风患者和346例健康对照者,检测中国汉族男性群体的IL-23受体内含子区rs7517847位点基因多态性分布,数据经,检验得出其与痛风发病的遗传易感性的关系。结果经,检验,痛风组和对照组中IL-23R基因rs7517847位点GG,GT和1Tr基因型频率（10．4％,49．5％,40．1％;16．2％,49．7％,34．1％;X^2=4．305,P〉0．05）与等位基因频率G和T（35．1％,41％;64．9％,59％;X^2=3．727,P〉0．05）均无统计学意义。IL-23R基因rs7517847位点G／T基因多态性与痛风病的危险因素无显著性关联。结论尚不能认为中国沿海地区汉族男性人群中IL-23R内含子区rs7517847位点基因多态性与痛风有关联性。     

载脂蛋白M基因多态性与兰州地区汉族人群风湿性疾病易感的相关性分析

目的研究载脂蛋白M(Apo M)基因多态性与兰州地区汉族人群类风湿性关节炎(RA)、系统性红斑狼疮(SLE)和强直性脊柱炎(AS)等疾病易感的相关性。方法针对Apo M基因的2个单核苷酸多态性(SNP)位点rs805296和rs805297设计引物,建立聚合酶链式反应-高分辨率融解曲线分析(PCR-HRM)基因分型方法,对599例RA、194例SLE、179例AS患者和273例健康对照进行病例对照研究,分析其与风湿性疾病易感的相关性。结果 rs805296位点在RA组、SLE组、AS组和健康对照组的基因型频率分别为AA 87.0%、AG 12.7%、GG 0.3%;AA 84.5%、AG 15.0%、GG 0.5%;AA 91.6%、AG 7.3%、GG1.1%;AA 85.0%、AG 15.0%、GG 0%。rs805297位点在RA组、SLE组、AS组和健康对照组的基因型频率分别为GG 38.2%、GT 51.8%、TT 10.0%;GG 44.3%、GT 45.4%、TT 10.3%;GG 37.4%、GT 47.5%、TT 15.1%;GG 40.7%、GT 46.1%、TT13.2%。统计学分析发现只有rs805296位点的基因型分布仅在AS组与健康对照组之间有明显差异,在显性模型下,rs805296位点G基因携带者(杂合突变型AG和纯合突变型GG)患AS的风险明显降低。结论本研究建立的PCR-HRM基因分型方法能够成功实现rs805296和rs805297位点的临床标本分子诊断,并发现rs805296位点与兰州地区汉族人群AS易感密切相关。     

白介素-23受体基因多态性与乙肝相关肝细胞癌的易感性研究

目的:探讨白介素-23受体(IL-23R)基因多态性与广西壮族人群乙肝相关肝细胞癌(HCC)易感性的关系。方法:采用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)对84例乙肝表面抗原(HBSAg)阳性HCC患者(病例组)和94例HbsAg阳性体检者(对照组)IL-23R基因rs10889677、rs1884444、rs114658173个位点的单核苷酸多态性进行检测及其部分标本进行直接测序鉴定。采用SHEsis软件构建IL-23R基因3个位点的单体型。Logistic回归分析IL-23R基因多态性和单体型与HCC遗传易感性的关系。结果:IL-23Rrs10889677、rs11465817位点的AA、AC、CC3种基因型和A、C两种等位基因在HCC组与对照组之间的分布差异无统计学意义(P>0.05)。rs1884444位点的TT、TG、GG三种基因型及T、G两种等位基因在病例组和对照组的频率分布差异均有统计学意义(P均<0.05),Logistic回归分析发现携带TG基因型的个体发生HCC的风险较携带TT基因型的个体增加(校正OR=2.20,95%CI=1.11～4.37)。单体型构建发现CGC、AGC、CTC、ATC、CGA、AGA、CTA、ATA等8种单倍体,病例组和对照组的AGC单倍体分布差异有统计学意义(P<0.05),AGC单倍体携带者发生HCC的风险明显增加(校正OR=2.71,95%CI=1.06～6.93)。结论:IL-23R基因rs1884444位点TG基因型可能是HCC发病的危险因子;乙肝背景下AGC单倍体携带者患HCC的风险增加2.71倍,可能是乙肝相关肝癌发病的危险因素。     

新生儿支气管肺发育不良TLR-10、SP-A1基因多态性及其与病情程度的关系

目的 探讨新生儿支气管肺发育不良（BPD）患儿Toll样受体10(TLR-10)、肺泡表面活性物质蛋白A1(SP-A1)基因多态性及其与病情程度的关系。方法 选取承德市中心医院83例BPD患儿作为观察组,另选取83例同期健康新生儿作为对照组。比较两组血清TLR-10、SP-A1水平、TLR-10rs11096955位点、SP-A1AA50位点基因多态性,分析两者基因多态性对BPD易感性的影响及与病情程度的关系。结果 观察组血清TLR-10、SP-A1水平高于对照组（P<0.05）;TLR-10 rs11096955位点、SP-A1 AA50位点基因型分布具有人群代表性。观察组与对照组TLR-10 rs11096955位点、SP-A1 AA50位点基因型、等位基因频率差异有统计学意义（P<0.05）;TLR-10 rs11096955位点AA基因型BPD易感性是AC/CC的1.401倍;SP-A1 AA50位点GG基因型BPD易感性是GC/CC的1.692倍;TLR-10 rs11096955位点AA基因型、等位基因A频率、SP-A1 AA50位点GG基因型、等位基因G频率与...     

内质网氨基肽酶-1基因(ERAP1)多态性与闽南地区汉族人群强直性脊柱炎关联性研究

本研究探讨内质网氨基肽酶-1基因(endoplasmic reticulum aminopeptidase 1,ERAP1)单核苷酸多态性与闽南地区汉族人群强直性脊柱炎(ankylosing spondylitis,AS)的相关性。选取经纽约诊断标准确诊的闽南地区汉族149例强直性脊柱炎患者(AS组)与150例健康人群(对照组),应用SNaPshot单碱基延伸反应测定所有研究对象ERAP1的10个SNP位点(rs26653、rs7711564、rs27980、rs30187、rs2287987、rs10050860、rs27529、rs17482078、rs27038、rs27044)基因型。结果显示,ERAP1的3个SNP位点rs27044(OR=1.324,P=0.001)、rs30187(OR=1.224,P=0.011)、rs27980(OR=1.220,P=0.005)位点基因型在闽南地区汉族人群AS组和正常对照组之间比较具有显著性差异(P0.05),其罕见等位基因是AS发病的危险因素,rs26653、rs7711564、rs2287987、rs10050860、rs27529、rs17482078、rs27038等SNP位点两组之间比较无统计学差异(P0.05)。本研究表明ERAP1基因单核苷酸多态性rs30187、rs27044、rs27980与闽南地区汉族人群强直性脊柱炎相关,进一步证实了该rs27044位点的等位基因(G)、rs30187位点的等位基因(T)、rs27980位点的等位基因(C)基因是强直性脊柱炎的易感基因。     

Interleukin-18基因启动子区单核苷酸多态性与肝细胞癌遗传易感性关系的研究

目的探讨白细胞介素18(IL-18)基因启动子区-607C/A(rs1946518)和-137G/C(rs187238)单核苷酸多态性(SNP)与肝细胞癌(肝癌)遗传易感性的关系。方法应用序列特异性引物-聚合酶链反应(PCR-SSP)技术,检测228例肝癌患者和300例健康对照者IL-18基因启动子-607C/A(rs1946518)、-137G/C(rs187238)单核苷酸多态性位点基因型,分析肝癌患者和对照组基因型频率和等位基因频率分布。结果肝癌组SNP位点rs187238 G等位基因的频率明显高于对照组(OR=1.1891,95%CI=1.0106-1.5633,P=0.026)。携带rs187238 GG基因型的肝癌患者较多(OR=1.5168,95%CI=1.1490-1.8322,P=0.010)。分层分析发现,rs1946518位点上AA基因型与肝癌发病的关联在饮酒的肝癌患者中更加显著(P=0.024),而且rs187238位点上GC/CC基因型与肝癌发病的关联在出现肝癌复发的患者中更加显著(P=0.005)。结论 IL-18基因启动子区-137G/C(rs187238)GG基因型与肝癌遗传易感性有关联。而rs1946518位点AA基因型和rs187238位点GC/CC基因型分别与肝癌患者饮酒和肝癌复发有关联。     

中国大陆汉族人群强直性脊柱炎患者骨保护素基因多态性研究

目的：通过骨保护素（OPG）基因单核苷酸多态性（SNPs）位点的筛查,分析中国大陆汉族人群中OPG基因多态性与强直性脊柱炎（AS）易感性的相关性。方法：采集2008年1月至2012年1月在我院就诊的AS患者195例（AS组）及203例性别、年龄与之匹配的健康体检者（对照组）的外周血样本,并提取基因组DNA。所有样本采用TaqMan探针法对OPG基因SNP rs2073618、rs4355801位点进行基因型鉴定。比较AS组与对照组之间不同等位基因及基因型的分布差异,并分析其与AS易感性的相关性。结果：OPG基因SNP rs2073618、rs4355801位点的等位基因及基因型分布均符合Hardy—Weinberg平衡。AS组与对照组等位基因频率分别如下。rs2073618（G）：71．0％、71．9％,（C）：29．0％、28．1％;rs4355801（G）：27．7％、26．4％,（A）：72．3％、73．6％。两组在基因型频率的分布上显示,m2073618（CC）：9．2％、8．9％,（GC）：39．5％、38．4％,（GG）：51．3％、52．7％;rs4355801（AA）：52．3％、52．7％,（AG）：40．0％、41．9％,（GG）：7．7％、5．4％。以上数据组间比较差异均无统计学意义（P〉0．05）。经关联性分析,未发现AS发病的风险等位基因或基因型。结论：中国大陆汉族人群中OPG基因SNP rs2073618、rs4355801单核苷酸多态性与AS的易感性之间没有相关性。     

IL-10、MD-1基因单核苷酸多态性与哮喘易感性的相关性研究

目的:分析IL-10基因 rs1800896、rs3024492位点和髓样分化蛋白1(Myeloid differentiation 1,MD-1)基因rs7740529、rs2233128位点单核苷酸多态性(Single nucleotide polymorphism,SNP)与哮喘遗传易感性的相关性以及过敏性鼻炎(Allergic rhinitis,AR)对哮喘遗传易感性的影响.方法:应用Sequenom MassARRAY○ R SNP分型技术对141例哮喘患者和145例正常对照的四个SNP位点(rs1800896、rs3024492、rs7740529、rs2233128)进行基因分型,再将哮喘患者中确定有过敏性鼻炎和无过敏性鼻炎者分别与正常对照组比较.χ2检验统计分析病例组和对照组的基因型频率;采用非条件Logistic回归校正年龄、性别影响,计算比数比(OR)和95%可信区间(CI),以此评价各位点多态性与哮喘遗传易感性的相关性以及过敏性鼻炎对哮喘易感性的影响.结果:(1)IL-10 rs1800896多态性位点GG、GA、AA三种基因型分布频率在哮喘组、哮喘和过敏性鼻炎共患组、哮喘而无鼻炎组的分布频率和对照组相比,差异均有统计学意义(P＜0.001),有无过敏性鼻炎对其影响不明显.相较GG或AA基因型,携带基因型GA的个体,哮喘的患病风险明显降低(OR=0.033,95%CI:0.017～0.065).(2)MD-1 rs7740529位点CC、CT、TT三种基因型分布频率在哮喘患者组、哮喘和过敏性鼻炎共患组、哮喘而无鼻炎组的分布频率和对照组相比,差异也均有统计学意义(P≤0.005),有无过敏性鼻炎对其影响不明显.相比较CC或TT基因型,携带基因型CT的个体,哮喘的患病风险明显降低(OR=0.369,95%CI:0.225～0.606).(3)IL-10 rs3024492位点TA、AA基因型和MD-1 rs2233128位点AG、GG基因型在哮喘人群中的分布频率与对照组相比无统计学意义(P＞0.05).结论:IL-10 rs1800896与MD-1 rs7740529位点多态性与哮喘的遗传易感性相关,其杂合型的患病风险均明显降低,且有无过敏性鼻炎对其影响不明显.     

VEGF基因单核苷酸多态性与中国北方汉族人SLE易感性的相关性研究

目的:研究血管内皮生长因子(VEGF)基因单核苷酸多态性(SNP)与中国北方汉族人系统性红斑狼疮(SLE)易感性的相关性。方法:应用Sequenom飞行时间质谱技术检测44例SLE患者和100例正常对照者外周血VEGF基因的SNPs,选择6个VEGF基因的SNP位点:rs2010963、rs3024994、rs3025000、rs3025010、rs3025035和rs833070进行基因分型,用SPSS 11.5软件对数据资料进行统计分析。结果:SLE患者VEGF多态性位点rs2010963、rs3024994、rs3025000、rs3025010、rs3025035的基因型频率及等位基因频率与正常对照组比较差异无统计学意义(P0.05);VEGFrs833070 A等位基因频率明显高于对照组(31.2%vs20%,χ2=4.547,P=0.033,OR=1.818,95%CI 1.045-3.162)。rs833070 G等位基因在SLE组中关节炎与无关节炎组中频率有显著差异(56%vs80.4%,χ2=5.613,P=0.018,OR=0.336,95%CI 0.134-0.843),rs833070 GG基因型频率明显低于无关节炎组(GGvsAG+AA:28%vs65.2%,χ2=6.684,P=0.010,OR=0.207,95%CI 0.061-0.705),而VEGF rs833070位点基因型、等位基因型的频率与患者血清中ds-DNA抗体、抗Sm抗体、狼疮性肾炎、间质性肺疾病的发生无相关性(P0.05)。结论:VEGF基因SNP点rs833070与北方汉族人SLE发病易感性相关,rs833070位点A等位基因可能增加了SLE患病的易感性,而rs833070 GG基因型及G等位基因型可能是SLE合伴关节炎的保护性基因。     

Interleukin 23 receptor: Expression and regulation in immune cells

The importance of IL-23 and its specific receptor, IL-23R, in the pathogenesis of several chronic inflammatory diseases has been established, but the underlying pathological mechanisms are not fully understood. This review focuses on IL-23R expression and regulation in immune cells.     

IL-23 Plasma level measurement in relapsing remitting multiple sclerosis (RRMS) patients compared to healthy subjects

Background: Multiple sclerosis (MS) is a chronic neuroinflammatory disease with unknown etiology and variable clinical evolution. Interleukin-23 (IL-23), a member of the IL-12 cytokine family is a heterodimeric cytokine composed of the IL-12p40 subunit, and with a novel p19 subunit, its ability to enhance the expansion of T helper type 17 (Th17) cells indicates the responsibility for many of the inflammatory autoimmune responses.

Objective: The objective of the project is to measure IL-23 level in plasma of multiple sclerosis (MS) patients in comparison with healthy control subjects.

Methods: In a case-control study, plasma was collected from healthy subjects as control group (n?=?40) and patients with relapsing remitting multiple sclerosis (RRMS) (n?=?40). The plasma level of IL-23 was assessed by ELISA method. Statistical analysis was performed with SPSS (Ver. 16).

Results: Plasma level of IL-23 in MS patients was significantly increased compared to control subjects (p Value?<?0.001).

Conclusions: Our findings revealed the increased IL-23 level in patients’ group. In conclusion, the inhibition of IL-23 might be a novel and promising therapeutic strategy, especially in the therapy of autoimmune inflammatory diseases. IL-23 plays a pivotal role in development of MS and might be a specific marker and therapeutic target for MS.     

Pathological significance and regulatory mechanism of lymphotoxin β receptor overexpression in T cells of patients with systemic lupus erythematosus

Systemic lupus erythematosus (SLE) is a typical autoimmune disease. Lymphotoxin β receptor (LTβR) signaling plays an important role in autoimmune inflammations. LTβR-Ig fusion protein, LTβR blocking agent, has been used to treat SLE, while its mechanism remains to be fully elucidated. In this study, to investigate the expression of LTβR in the T cells of SLE patients and its roles in the pathogenesis of SLE, we isolated the peripheral blood T cells of SLE patients and normal controls to detect expression of LTβR by flow cytometry and RNA assay. T cells were also stimulated with LIGHT, a ligand of LTβR, and then detected for their LTβR expressions and apoptosis by flow cytometry. Also, their expressions of inflammatory factors and receptors were determined by RNA assay. The results showed that LTβR positive cells were 22.75%
6.98% in CD3+ cells of SLE patients, while there were almost no LTβR positive cells in CD3+ cells of normal persons. Moreover, LTβR expression was remarkably higher in CD3, CD4 and CD8 positive T cells of active SLE patients than non/low active patients (all P < 0.05), and positively correlated with increased Ig level, decreased complement level and renal damage. Moreover, the stimulation of SLE T cells with LIGHT promoted higher expression of LTβR, IL-23R and IL-17A, and apoptosis of T cells. In conclusion, we demonstrated a high expression of LTβR in the T cells of SLE patients which may be associated with pathogenesis of SLE.     

Ablation of Systemic Phosphate‐Regulating Gene Fibroblast Growth Factor 23 (Fgf23) Compromises the Dentoalveolar Complex

Fibroblast growth factor‐23 (FGF23) is a hormone that modulates circulating phosphate (P_i) levels by controlling P_i reabsorption from the kidneys. When FGF23 levels are deficient, as in tumoral calcinosis patients, hyperphosphatemia ensues. We show here in a murine model that Fgf23 ablation disrupted morphology and protein expression within the dentoalveolar complex. Ectopic matrix formation in pulp chambers, odontoblast layer disruption, narrowing of periodontal ligament space, and alteration of cementum structure were observed in histological and electron microscopy sections. Because serum P_i levels are dramatically elevated in Fgf23^?/?, we assayed for apoptosis and expression of members from the small integrin‐binding ligand, N‐linked glycoprotein (SIBLING) family, both of which are sensitive to elevated P_i in vitro. Unlike X‐linked hypophosphatemic (Hyp) and wild‐type (WT) specimens, numerous apoptotic osteocytes and osteoblasts were detected in Fgf23^?/? specimens. Further, in comparison to Hyp and WT samples, decreased bone sialoprotein and elevated dentin matrix protein‐1 protein levels were observed in cementum of Fgf23^?/? mice. Additional dentin‐associated proteins, such as dentin sialoprotein and dentin phosphoprotein, exhibited altered localization in both Fgf23^?/? and Hyp samples. Based on these results, we propose that FGF23 and (P_i) homeostasis play a significant role in maintenance of the dentoalveolar complex. Anat Rec 293:1214–1226, 2010. © 2010 Wiley‐Liss, Inc.     

Anti-CD23

CD23, the low-affinity immunoglobulin (Ig)E receptor (FcεRII), is widely distributed on the surface of various human cells. CD23 mediates numerous IgE-related immune responses (including allergen focusing) by enhancing IgE antigen complex presentation, regulating IgE synthesis, influencing cell differentiation and growth of both B- and T-cells, and stimulating production of pro-inflammatory mediators from monocytes/macrophages, eosinophils, and even airway smooth muscle cells. Both membrane and soluble CD23 play an important role in allergic reactions. Cellular contacts and cytokines modulate its expression in a concerted manner as needed for allergic reactions. Expression of CD23 and soluble CD23 has been associated with allergic diseases. Targeting CD23 with monoclonal antibody (MAb) is a promising candidate therapy in allergic diseases. A newly developed agent known as Lumiliximab, which is an anti-CD23 MAb (Lumiliximab), was demonstrated to be a well-tolerated agent in a phase I clinical trial (a placebo-controlled study with allergic asthma). Adverse events were mild, and no relationship was apparent between the dose of Lumilixilab and the frequency, severity, or type of event. Sustained and dose-dependent decreases in mean serum total IgE concentrations were noted. The serum half-life of Lumilixilab increased from 2 to 10 d with increasing doses. Blocking antigen presentation, preventing costimulation signals, and reducing production of pro-inflammatory mediators are some of the potential mechanisms involved for anti-CD23 activity. Although the safety and clinical efficacy of Lumilixilab in allergic asthma and rhinitis require confirmation, the observed data imply that anti-CD23 is a promising candidate therapy option for future treatment of allergic diseases.     

人rBPI23在大肠杆菌DH5α中的表达及其多克隆抗体的制备

目的制备人rBPI23蛋白并免疫家兔获得特异性多克隆抗体。方法将本室制备的pBV220-synBPI600表达载体转化感受态E.coliDH5α,温控诱导后,获得以包涵体形式表达的目的重组蛋白;用SDS-PAGE鉴定分子质量,West-ernblot鉴定抗原性;免疫家兔获得抗rBPI23抗血清,经饱和硫酸铵沉淀获得多克隆抗体,间接法ELISA检测抗体效价,Westernblot分析抗体的特异性。结果重组蛋白主要以包涵体形式表达,SDS-PAGE显示其分子质量约23ku,与预期结果相符;重组蛋白能与市售兔抗人BPI抗体特异性结合;免疫家兔获得高效价(1∶320000)抗血清,上述抗体能与rBPI23及人BPI标准品特异性结合。结论成功制备了人rBPI23,免疫家兔获得高效价抗人rBPI23多克隆抗体,为制备单克隆抗体及后期建立BPI免疫学检测方法奠定基础。     

Jacobsen distal 11q deletion syndrome with a myelodysplastic change of hemopoietic cells

We describe a male infant with unusual facial appearance, relative pancytopenia, bilateral simian creases, and an accessory nipple. Cytogenetic analysis showed deletion of the long arm of chromosome 11 [46,XY,del(11)(pter→q23.2:)]. Bone-marrow study showed a myelodysplastic change of hemopoietic cells compatible with peripheral blood findings. Pachygyria of the temporal and frontal lobes was demonstrated by magnetic resonance image (MRI) of the brain. We present our findings in order to contribute to the information on 11q23 deletion. Am. J. Med. Genet. 75:341-344, 1998. © 1998 Wiley-Liss, Inc.     

靶向23S rRNA的多肽核酸体外抑制细菌蛋白翻译

目的 尝试研究反义多肽核酸（peptide nucleic acid，PNA）在体外翻译系统中抑制细菌蛋白的翻译。方法以增强绿色荧光蛋白（enhanced green fluorescent protein，EGFP）为报告分子，将重组载体pET-28a—EGFP和靶向23S rRNA domainⅡ区的PNA在体外翻译系统中共同孵育后，用荧光显微镜观察荧光强度减弱，放射自显影证明荧光强度减弱是因为EGFP减少。为了分析PNA体外抑制蛋白翻译的浓度，我们用蛋白沉淀方法分析PNA体外抑制[^35S]methionine渗入蛋白比例。最后，用浊度分析观察PNA（G1138）在MH肉汤培养基中的抑菌作用。结果在体外翻译系统中，靶向23S rRNA do-mainⅡ区的PNA（G1138）以剂量和序列依赖方式抑制蛋白合成，抑制浓度（IC50）为0．15μmol／L。在MH培养基中，PNA（G1138）抑菌效果不明显（MIC〉50μmol／L）。结论靶向23S rRNA domainⅡ区的PNA（G1138）在体外翻译系统中能有效抑制细菌蛋白合成。在MH肉汤培养基中，PNA（G1138）抑菌效果不明显。