湖北食管癌HLA-DQB1的基因多态性

目的从基因水平探讨湖北地区汉族人食管癌HLA-DQB1等位基因的遗传易感性.方法运用序列特异性引物聚合酶链反应技术,检测无亲缘关系湖北汉族健康人136例、食管癌组42例患者的HLA-DQB1等位基因.SAS system统计软件数据处理.结果湖北汉族人食管癌患者与正常人比较,HLA-DQB1*0301基因频率显著增高(0.2976vs0.1875),P=0.046,OR=1.835,病因分数=0.1354);两组间HLA-DQB1其余各等位基因分布频率的比较,HLA-DQB1*0201(0.0833 vs 0.1016),*0301(0.2976 vs 0.1875),*0302(0.0595 vs 0859),*0303(0.2381 vs 0.1875),*0304(0.0000 vs 0.0039),*0401(0.0714 vs 0.0469),*0402(0.0119 vs 0.0156),*0501(0.0357 vs 0.0703),*0502(0.0595 vs 0.0664),*0503(0.0119 vs 0.0195),*0504(0.0000 vs 0.0039),*0601(0.0595 vs 0.0781),*0602(0.0476 vs 0.0742),*0603(0.0000 vs 0.0078),*0604(0.0238 vs 0.0508),差异均无显著性.结论 HLA-DQB1*0301等位基因与湖北汉族人食管癌正关联,为其易感基因.林军,邓长生,孙洁,周燕,熊平,汪亚平.湖北食管癌HLA-DQB1的基因多态性.世界华人消化杂志,2000;8(9):965-968     

HLA-DQB1基因多态性与扩张型心肌病遗传易感性研究

扩张型心肌病(DCM)是在一定遗传易感性的基础上,病毒感染诱发的免疫性心肌损伤。这种抗自身组织的异常免疫应答是由于病毒诱导心肌细胞抗原暴露,人类白细胞抗原(HLA)-Ⅱ类分子异常表达,将自身抗原信息传递给T淋巴细胞,引起心脏自身免疫损伤。HLA限制T细胞受体识     

HLA-DQB1基因多态性与重症肌无力遗传易感性的关系

2001～2003年，我们运用PCR-SSP方法对中国北方地区49例重症肌无力(MG)与HLA-DQB1的相关性进行分析，以期进一步探讨MG免疫学异常的机制，并为寻找MG的易感基因提供线索。     

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。     

1型糖尿病与HLA-DQB1基因及自身抗体相关性研究

采用基因分型技术,确定32例1型糖尿病患者及23例正常对照的HLA-DQB1等位基因.用酶联免疫吸附法测定血清中谷氨酸脱羧酶抗体(GADA)、胰岛细胞抗体(ICA)及胰岛素自身抗体(IAA).结果在1型患者中,DQB1*0201、*0303、*0604等位基因频率显著高于对照(P＜0.05),DQB1*0301则低于对照(P＜0.05),其余DQB1等无显著性差异.等位基因为DQB1*0201的患者中GADA阳性率显著高于阴性率.结论在中国汉族人群中,DQB1*0201、*0303、*0604是1型糖尿病易感性等位基因,DQB1*0301是1型糖尿病保护性等位基因.DQB1*0201可能对GADA的产生起允许作用.     

HLA-DR.DQ基因与骨关节结核的易感性研究

目的 探讨HLA-DR.DQ基因多态性与骨关节结核的遗传关联性,比较骨关节结核与肺结核之间易感基因的差异。方法 采用聚合酶链反应-序列特异性引物 (PCR-SSP)方法,对86例骨关节结核,88例正常人及34例肺结核的HLA-DR.DQ等位基因进行分析。结果 骨关节结核组与正常人比较,骨关节结核组DRB109、DQB10301基因频率增高 (38.99%比8.24%　PC ＜0.0001　RR =8.92;18.27%比2.66%　PC ＜0.05　RR =2.21),DRB113.2基因频率显著低于对照组 (4.76%比20.50%　PC ＜0.001　RR =0.18)。骨关节结核组与肺结核比较,DRB109、DQB10301基因频率增高 (38.99%比9.2%　PC ＜0.0001;18.15%比1.85%　PC ＜0.001),而DRB115基因频率低于肺结核组 (17.17%比36.3%　PC ＜0.01)。结论 HLA-DRB109、DQB10301可能是我国骨关节结核的易感基因,DRB113.2为保护基因。骨关节结核与肺结核之间易感基因存在差异。     

人类白细胞抗原DRB1基因与肺结核的相关性研究

目的探讨HLA-DRB1基因多态性与肺结核(PTB)的遗传关联性及其与临床表现的关系。方法采用聚合酶链反应-序列特异性引物(PCR-SSP)方法,对74例PTB患者及90名正常人的HLA-DRB1等位基因进行分型。结果与对照组相比,PTB病例组的DRB1*15等位基因频率显著增高(34.3%比17.0%,Pc<0.05,RR=2.91),HLA-DRB1*12基因频率高(15.4%比7.5%),但统计学上无显著性差异(Pc>0.05);而DRB1*11基因频率显著低于对照组(1.4%比9.9%,Pc<0.05,RR=0.12)。HLA-DRB1*15阳性患者中复治病例数和耐药病例数均显著高于HLA-DRB1*15阴性组(P<0.05)。结论HLA-DRB1*15可能是PTB的易感基因,DRB1*11可能为保护基因,HLA-DRB1*15基因与PTB临床特征有一定相关性。     

壮族人2型糖尿病HLA—DQA1基因遗传易感性的研究

目的：探讨壮族2型糖尿病患者（DM）及其并发症与人类白细胞抗源（HLA）的相关性。方法：采用聚合酶链反应－序列特异性引物（PCR－SSP）法,对40例壮族2型DM患者和82名壮族正常人HLA－DQA1位点进行基因分型研究。结果：壮族人2型DM组DQA1＊0104等位基因频率明显低于对照组（P＜0．001）,DQA1＊0401等位基因频率明显高于对照组（P＜0．001）。结论：壮族2型DM与HLA有关联,壮族和汉族2型DMA与HLA有不同的关联格局。     

白血病患者Prame基因的表达及其与WT1基因比较的临床意义

目的：探讨Prame(黑色素瘤特异性抗原)在白血病患者中的表达及其临床意义。方法：应用逆转录—聚合酶链反应(RT—PCR)测定58例白血病患者Prame mRNA的表达，并与WTl mRNA的表达相比较。结果：急性髓细胞性白血病(AML)患者Prame阳性表达率为52．2％，急性淋巴细胞性白血病(ALL)患者Prame阳性表达率为66．7％，慢性粒细胞性白血病(CML)急性变患者Prame阳性表达率为55．6％；慢性及加速期CML患者ll例、l0名正常人外周血及l0例非血液病患者骨髓细胞均未见Prame mRNA表达，其中l例AML和5例ALL患者Prame阳性而WT1阴性。对2例Prame阳性和4例Prame、WTl均阳性的患者短期随访发现所有患者化疗后Prame均有不同程度的下降。l例复发患者Prame表达再次升高且早于WTl l个月，余3例白血病患者Prame和WTl表达的波动呈正比。结论：免疫抗原Prame是白血病的一个重要标记基因，与病程进展密切相关，有望成为白血病微小残留病灶检测和进行白血病免疫治疗的靶基因。     

徐州地区汉族人及慢性乙型肝炎HLA-A基因多态性的研究

探讨慢性乙型肝炎与HLA-A位点的等位基因多态性.用PCR-SSP方法对徐州地区汉族正常组和慢性乙型肝炎组的HLA-A基因多态性进行分析.HLA-A＊0201-17出现的频率在慢性乙型肝炎组为45.57%,高于正常组的29.69%,P=0.002＜0.05,RR=1.983,（95%CI：1.227-3.080）,具有统计学意义.HLA-A＊0201-17与慢性乙型肝炎较高的相关性,可能为易感基因.     

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.     

中国北方汉族人群HLA-A、HLA-B、HLA-DR等位基因频率检测及其临床意义

目的从基因水平了解中国北方地区汉族人群人类白细胞抗原HLA—A、HLA—B、HLA—DR位点的等位基因(以下分别简称为A等位基因、B等位基因及DR等位基因)频率,获得更完整、准确的HLA群体遗传学数据。方法应用聚合酶链反应一序列特异性引物(PCR—SSP)方法对2000名北方汉族健康志愿者进行A、B、DR等位基因分型。结果鉴定了17个A等位基因,32个B等位基因,13个DRB1等位基因。最常见的基因型分别为A^ 02、B^ 13、DRB1^ 15,其相应基因频率范围分别为0．2400～0．2767、0．1330～0．1432和0．1557～0．1707。结论本结果可作为我国HLA多态性研究的群体资料和正常参考值,对群体遗传、疾病关联研究以及寻找HLA相合的异基因造血干细胞供者具有重要意义。     

HLA-DRB1、-DQB1基因多态性与食管鳞癌遗传关联性

目的　从基因水平探讨食管鳞癌HLA DRB1 , DQB1等位基因的遗传易感性 ,以阐述其免疫遗传学特征。方法　运用序列特异性引物聚合酶链反应技术 ,检测无亲缘关系湖北汉族健康人 1 36例、食管鳞癌患者 42例的HLA DRB1 , DQB1等位基因。结果　湖北汉族人食管鳞癌患者与正常人比较 ,HLA DRB1 0 90 1等位基因分布频率显著增高 (0 .2 50 0比 0 .1 397,P =0 .0 2 8,OR =2 .0 53 ,病因分数 =0 .1 2 82 ) ,HLA DQB1 0 30 1基因分布频率显著增高 (0 .2 976比 0 .1 875 ,P =0 .0 4 6 ,OR =1 .835 ,病因分数 =0 .1 35 4)。两者间其余HLA DRB1、 DQB1等位基因分布频率差异均无显著性。结论　HLA DRB1 0 90 1及 DQB1 0 30 1等位基因均与食管鳞癌正关联 ,为其易感基因。该两等位基因测序结果与其基因库第 2外显子序列吻合。     

HLA—DRB1、DQB1基因多态性与流行性出血热的相关性

目的从基因水平探讨HLA—DRB1、DQB1等位基因多态性与流行性出血热的相关性,以阐述其免疫遗传学特征。方法应用序列特异性引物聚合酶链反应技术检测流行性出血热患者和正常对照组各50例的HLA—DRB1、DQB1等位基因。结果流行性出血热患者与正常对照组比较,HLA—DRB1＊16等位基因分布频率明显增高（Pc=0．0106）,两组间其余HLA-DRB1、-DQB1等位基因分布频率差异无统计学意义（Pc〉0．05）。结论HLA-DRB1＊16等位基因与流行性出血热呈正相关,可能为流行性出血热易感基因之一。     

The relation between HLA-DQA1 genes and genetic susceptibility to duodenal ulcer in Wuhan Hans

AIM To study the genetic susceptibility of HLA-DQA1 alleles to duodenal ulcer in Wuhan Hans.METHODS Seventy patients with duodenal ulcer and fifty healthy controls were examined for HLA-DQA1 genotypes. HLA-DQA1 typing was carried out by digesting the locus specific polymerase chain reaction amplified products with alleles specific restriction enzymes (PCR-RFLP), i.e., Apal Ⅰ, Bsaj Ⅰ, Hph Ⅰ, Fok Ⅰ,Mbo Ⅱ and Mnl Ⅰ.RESULTS The allele frequencies of DQA1 * 0301 and DQA1* 0102 in patients with duodenal ulcer were significantly higher and lower respectively than those in healthy controls (0.40 vs 0.20,P=0.003, Pcorret = 0.024) and (0.05 vs 0.14,P= 0.012, but Pcorret ＞0.05), respectively.CONCLUSION DQA1* 0301 is a susceptible gene for duodenal ulcer in Wuhan Hans, and there are immunogenetic differences in HLA-DQA1 locus between duodenal ulcer patients and healthy controls.     

Herpes simplex virus type 1 in peptic ulcer disease： An inverse association with Helicobacterpylori

AIM: To assess the frequency of herpes simplex virus type I in upper gastrointestinal tract ulcers and normal mucosa with the modern and better assays and also with a larger number of well characterized patients and controls and its relationship to Helicobacter pylori(H pylori). METHODS: Biopsy specimens from 90 patients (34 with gastric ulcer of the prepyloric area and 56 with duodenal ulcer) were evaluated. Biopsies from 50 patients with endoscopically healthy mucosa were considered as the control group. The method used to identify herpes simplex virus-1 (HSV-1) was polymerase chain reaction. H pylori was detected by the CLO-test and by histological method. RESULTS: Herpes simplex virus-1 was detected in 28 of 90 patients with peptic ulcer (31%) [11 of 34 patients with gastric ulcer (32.4%) and 17 of 56 with duodenal ulcer (30.4%)] exclusively close to the ulcerous lesion. All control group samples were negative for HSV-1. The likelihood of H pylori negativity among peptic ulcer patients was significantly higher in HSV-1 positive cases than in HSV-1 negative cases (P = 0.009). Gastric ulcer patients with HSV-1 positivity were strongly associated with an increased possibility of Helicobacter pylori negativity compared to duodenal ulcer patients (P = 0.010). CONCLUSION: HSV-1 is frequent in upper gastrointestinal tract ulcers but not in normal gastric and duodenal mucosa. There is an inverse association between HSV-1 and H pylori infection.     

三叶因子2基因治疗对实验性大鼠胃溃疡愈合影响的研究

目的探讨三叶因子2(TFF2)基因治疗对实验性大鼠胃溃疡的疗效及其机制。方法2005-06-10—2006-03-15南方医科大学南方医院消化病研究所将48只雄性Wistar大鼠随机分为2组,治疗组24只,对照组24只。治疗组每只应用pcDNA3.1g TFF2100μg,对照组每只应用等容积pcDNA3.1g TFF2100μg,均在造模时经胃壁浆膜下注入。用药后分别在第3、7、14天处死动物,测量大鼠胃溃疡指数、胃总酸度及黏液糖蛋白量的变化。结果在应用pcDNA3.1g TFF2的第3天,治疗组和对照组比较,各项指标差异无统计学意义(P>0.05);第7天,治疗组的黏液糖蛋白量显著增加,与对照组比较差异有统计学意义(P<0.01)。第14天,治疗组的溃疡面积显著缩小,与对照组比较差异有统计学意义(P<0.01);治疗组黏液糖蛋白量有所下降,不过与对照组比较差异也有统计学意义(P<0.05);而治疗组的胃总酸度变化不大,与对照组比较差异无统计学意义(P>0.05)。结论TFF2基因治疗对实验性大鼠胃溃疡愈合有促进作用,增加胃黏液糖蛋白的分泌是其促进溃疡愈合的机制之一,而与抑制胃酸分泌无关。     

Evidence for the role of gastric mucosa at the secretion of soluble triggering receptor expressed on myeloid cells （strem-1） in peptic ulcer disease

AIM: To investigate the role of gastric mucosa at the secretion of sTREM-1 in peptic ulcer. METHODS: Seventy two patients were enrolled; 35 with duodenal, 21 with gastric ulcer and 16 with chronic gastritis. Patients were endoscoped and gastric juice was aspirated. Patients with duodenal and gastric ulcer underwent a second endoscopy post-treatment. Biopsies were incubated in the absence/presence of endotoxins or gastric juice. Supernatants were collected and sTREM-1 and TNFα were measured by enzyme immunoabsorbent assays. Scoring of gastritis was performed before and after treatment according to updated Sydney score. RESULTS: Patients with duodenal and gastric ulcer and those with chronic gastritis had similar scores of gastritis. sTREM-1 was higher in supernatants of tissue samples of H pylori-positive than of H pylori-negative patients with gastric ulcer. Median (± SE) sTREM-1 was found increased in supernatants of patients with gastric ulcer before treatment (203.21 ± 88.91 pg/1000 cells) compared to supernatants either from the same patients post-treatment (8.23 ± 5.79 pg/1000 cells) or from patients with chronic gastritis (6.21 ± 0.71 pg/1000 cells) (P < 0.001 and < 0.001, respectively). Similar differences for sTREM-1 were recorded among LPS-stimulated tissue samples of patients (P = 0.001). Similar differences were not found for TNFα. Positive correlations were found between sTREM-1 of supernatants from patients withboth duodenal and gastric ulcer before treatment and the degree of infiltration of neutrophils and monocytes. CONCLUSION: sTREM-1 secreted by the gastric mucosa is an independent mechanism connected to the pathogenesis of peptic ulcer. sTREM-1 was released at the presence of H pylori from the inflamed gastric mucosa in the field of gastric ulcer.     

Protective role of metallothionein in stress-induced gastric ulcer in rats

AIM: To illustrate the pathophysiological role of metallothionein (MT) in gastric ulcer induced by stress. METHODS: Wistar rats underwent water-immersionrestraint (WIR) stress, ZnSO_4 (an MT inducer) treatment, WIR+ZnSO_4 or WIR+MT, and the ulcer index (UI) was estimated in excised stomach and liver tissues. The mRNA level of gastric MT was determined by semi-quantitative RT-PCR. The MT content in gastric and hepatic tissues was determined by Cd/hemoglobin affinity assay. The lipid peroxidation products malondialdehyde (MDA) and conjugated dienes (CD) were estimated by use of thiobarbituric acid reactive species and ultraviolet spectrophotometry. RESULTS: WIR stress induced severe gastric mucosal lesions in rats. Compared with control rats, stressed rats had increased lipid peroxide content in serum and stomach and liver tissues. MDA content was increased by 34%, 21% and 29% and CD level by 270%, 83% and 28%, respectively. MT content in the stomach and liver was increased by 0.74- and 1.8-fold, and the MT-mRNA level in the stomach was increased by 26%. Pretreatment with ZnSO_4 prevented gastric lesion development (the UI was 87% lower than that without pretreatment), and the MDA and CD content in serum and tissues was lower. The MT content in the liver was double in rats that were not pretreated, and the MT mRNA level in the stomach was 35% higher. MT administration 1 h before the WIR stress prevented gastric lesion development (the UI decreased by 47% compared with that in rats not pretreated), and the MDA and CD content in serum and tissues was significantly lower. CONCLUSION: In WIR-stressed rats, the MT level was increased in serum and in stomach and liver tissues. Pre-administration of exogenous MT or pre-induction of endogenous MT can protect the gastric mucosa against stress-induced ulcers and inhibits the formation of stressinduced lipid peroxide. MT could have a gastroprotective effect and might be a new interventive and therapeutic target in stress-induced gastric ulcers.