MICA第5外显子微卫星多态性与食管癌相关性研究北大核心CSCD

目的:研究MICA第5外显子微卫星多态性与食管癌相关性。方法:采用PCR-STR微卫星基因分型技术检测103例食管癌患者和84例正常对照MICA基因5外显子多态性。构建食管癌标本中高频率出现的MICA等位基因的真核表达载体,转染293T细胞株,LDH法检测NK细胞对不同MICA等位基因转染的293T细胞的杀伤作用,效靶比20∶1。ELISA法检测转染的293T细胞上清中s MICA含量。结果:食管癌患者第5外显子检测到5种等位基因,频率分别为:MICA-A4(9.71%),MICA-A5(22.3%),MICA-A5.1(40.8%),MICA-A6(15.5%),MICA-A9(11.7%),其中MICA-A5.1与对照组对比差异有统计学意义(P<0.05)。MICA等位基因转染293T细胞株后,相对于其他第5外显子A5.1组对NK杀伤的敏感性较低[(30.4±6.3)%,P<0.05],上清可溶性MICA分泌增加(135.7±6.2)pg/ml。结论:食管癌与MICA第5外显子多态性A5.1显著性相关,其危险性高于其他等位基因。     

上海汉族人群MICA基因第5外显子微卫星多态性研究

目的 了解上海地区汉族人群ＭＩＣＡ基因第５外显子微卫生多态性分布,以及ＭＩＣＡ基因与其紧密连锁的ＨＬＡ－Ｂ基因位点的关系。方法 用ＰＣＲ－异源双链分析法,对１７５名正常无关个体的ＭＩＣＡ基因第５外显子微卫星多态性的分布进行研究。结果 （１）上海地区汉族人群ＭＩＣＡ基因第５外显子存在５种等位基因,其中ＭＩＣＡ＊Ａ５最为常见（３９．１４％）,其次为＊Ａ５．１（２２．２９％）;（２）ＭＩＣＡ等位基因与Ｈ     

MICA基因多态性与肺癌的相关性研究

目的 研究海南汉族人群MICA基因的多态性与肺癌的相关性.方法 采用PCR-SSP和PCR-SBT方法对样本MICA基因的多态性进行检测分析.结果 肺癌患者中有1 1种MICA等位基因被检测出来,MICA* A5/010基因频率在肺癌组中明显增高(MICA* A5:OR=1.62,95％ CI:1.18～2.23,Pc ＜0.05;MICA *010:OR=6.13,95％ CI:3.5～10.75,Pc＜0.000).结论 MICA* A5/010基因可能与肺癌的易感性相关.     

MICA基因多态性及血清可溶性MICA浓度与结肠癌的相关性研究

目的 观察主要组织相容性复合体Ⅰ类相关基因A(major histocompatibility complex class Ⅰ chain-related gene A,MICA)全长多态性与结肠癌的发病是否关联,以及血清可溶性主要组织相容性复合体Ⅰ类相关抗原A(major histocomptctibility complex class Ⅰ chain-related antigen A,MICA)浓度与结肠癌发病及病程的相关性.方法 应用聚合酶链反应-序列特异性引物及DNA测序分型方法,分析江苏扬州地区117例结肠癌患者和113名健康个体的MICA基因全长多态性及其编码分子第129位氨基酸残基的变化.血清可溶性MICA浓度通过酶联免疫吸附试验方法测定.结果 结肠癌患者和正常群体胞外区和跨膜区MICA等位基因的分布差异均无统计学意义,MICA跨膜区等位基因在不同病期结肠癌患者的分布差异亦无统计学意义.而结肠癌患者群体内MICA第129位氨基酸残基为蛋氨酸的频率显著降低;可溶性MICA浓度在Duke's C和D期患者血清内显著升高.结论 MICA等位基因多态性与结肠癌的发病及进展没有关联,但血清可溶性MICA浓度的检测可作为判断结肠癌预后的指标之一.     

广东汉族人群MICA和MICB微卫星多态性分布

目的　调查广东地区汉族人群 MICA基因第 5外显子和 MICB基因第 1内含子微卫星多态性分布。方法　应用聚合酶链反应和荧光 ( 6 - FAM)自动化检测技术 ,对广东地区共 10 6名无亲缘关系样本进行 MICA和 MICB微卫星基因分型 ,并计算这两个微卫星的基因频率、基因型频率、个体鉴别力、期望杂合性、多态性信息含量和非父排除率。结果　MICA和 MICB微卫星基因型分布符合 Hardy- Weinberg平衡。MICA A5基因频率最高为 0 .2 877,A4基因频率则最低为 0 .132 1;A5 - 5 .1( 14 .15 % )和 A5 - 5 ( 10 .38% )基因型分布频率较高。 MICB CA14等位基因频率最高为 0 .32 5 5 ,CA19、CA2 8等位基因频率最低为0 .0 0 4 7,未检出 CA2 7。 CA14 - CA14 ( 14 .15 % )基因型分布频率较高。结论　 MICA基因第 5外显子和MICB基因第 1内含子微卫星适合作为中国人群的遗传标志 ,用于人类学、遗传疾病基因连锁分析、法医学亲子鉴定和个体识别等研究领域     

三个群体MICA基因外显子2、3和4的多态性研究

目的 调查上海地区汉族、云南傣族和新疆维吾尔族3个群体MICA基因外显子2、3和4的多态性。方法 采用聚合酶链反应－序列特异的寡核苷酸探针杂交（polymerase chain reaction and sequence-specific oligonucleotide robing,PCR-SSOP）方法，分析183名汉族、41名傣族和66名维吾尔族正常人群的MICA胞外区等位基因多态性。结果 分别在汉族、傣族和维吾尔族中检测出10、7和9个MICA等位，其中MICA^*008在汉族和维吾尔族中频率最高，而傣族中MICA^*010的频率最高。3个民族MICA等位基因分布方式各不相同，而且维吾尔族的等位基因分布与另外两个民族相比，差异具有显著性。结论 MICA等位基因分布方式具有民族地区特异性。     

TNFβ基因微卫星多态性与Graves病的相关性研究

目的 研究Graves病患者TNF(tumor necrosis factor)β基因第一内含子的微卫星多态性(TNFc)，分析TNFc与Graves病发病的关联，进一步探讨Graves病的发病机制。方法 选取Graves病实验组和正常对照组患者各36例，应用聚合酶链反应(PCR)技术，扩增具有微卫星多态性的TNFβ基因第一内合于，通过聚丙烯酰胺凝胶电泳，分析两组的基因频率和基因型频率。结果 TNFc微卫星多态性合有两个等位基因(TNFcl和TNFc2)及三种基因型(纯合于TNFclcl和TNFc2c2，亲合于TNFclc2)；Graves病实验组的TNFc2基因频率高于正常对照组，有显著性差异(x^2=4，02，P＜0．05)，TNFclcl基因型频率在Graves病实验组与正常对照组无显著性差异(X^2=2．72，P＞0．05)。结论 TNFc2等位基因与Graves病发病的易感性有关联，TNFclcl基因型在Graves病发病的遗传基础中不起重要作用。     

强直性脊柱炎患者MICA基因第2、3和4外显子的多态性及其与HLA-B抗原的连锁不平衡

目的探讨皖籍汉族人群MICA基因（major histocompatibility complex class Ⅰchain-related gene A，MICA）第2、3、4外显子的多态性，及其与HLA-B抗原的连锁不平衡在强直性脊柱炎（ankylosing spondylitis，AS）发病中的作用。方法采用聚合酶链反应-序列特异性寡核苷酸探针杂交（polymerase chain reactionsequence-specific oligonucleotide probing，PCR-SS0）技术对56例AS患者和112名正常对照人群进行MICA基因第2、3、4外显子的多态性和HLA-B抗原的检测。结果AS患者和正常对照人群的MICA等位基因分布均以MICA＊008占优势，频率分别为32．14％和30．36％。两组人群MICA＊007等位基因的分布差异有统计学意义（X^2=10．18，P〈0．05，RR=2．50）。单倍型分析显示，AS患者和正常对照人群的MICA等位基因均显示出与多个HLA-B位点的连锁不平衡现象，两组间差异有统计学意义的单倍型为MICA＊007-B27（X^2=18．46，P〈0．05，RR=7．47）。分层分析结果显示，HLA-B27阳性与AS的相关性有统计学意义（P〈0．05），但MICA＊007基因与AS的相关性无统计学意义（P〉0．05）。结论AS患者中MICA＊007等位基因频率的显著升高可能源于MICA基因与HLA-B位点间的广泛连锁不平衡。     

湖南地区鼻咽癌MHC-Ⅰ类链相关基因A第5外显子微卫星多态性研究

目的研究MHC-Ⅰ类链相关基因A(MHC class-Ⅰ chain related gene A, MICA)第5外显子微卫星多态性与湖南地区鼻咽癌之间的相关性.方法应用荧光聚合酶链反应-基因扫描技术和聚合酶链反应-序列特异性引物技术分析127例湖南地区鼻咽癌患者和112名正常人群MICA基因第5外显子微卫星等位基因及MICA基因缺失(MICA*Del)频率.结果 MICA*A9表型频率在患者组(45/127)高于对照组(20/112),相对风险值(relative risk)为2.524(P=0.001,Pc=0.006);MICA*A5.1表型频率在患者组(51/127)低于对照组(69 /112),相对风险值为0.418(P=0.0004, Pc=0.0026).进一步分析发现,MICA*A9在男性患者组的表型频率(35/101)高于男性对照组(11/78),相对风险值为3.23(P=0.00095,Pc=0.006);MICA*A5.1在男性患者组的表型频率(39 /101)低于男性对照组(49/78),相对风险值为0.372 (P=0.0007,Pc=0.004);各MICA-STR 等位基因频率在女性患者组与女性对照组之间的差异无统计学意义(Pc＞0.05).结论湖南地区MICA-STR等位基因多态性与鼻咽癌相关,MICA*A9是该人群男性个体的一个鼻咽癌遗传易感标记.     

湖南汉族人群MICA基因多态性分析

为了解湖南地区汉族人群MICA基因第2、3和4外显子多态性分布特点,采用PCR-SSP方法对162名无亲缘关系湖南汉族人群MICA等位基因进行分析。结果显示:在湖南汉族人群中共检测出12个等位基因和28种基因型,各等位基因分布频率有差异,其中以MICA*00801基因频率最高(37.9%),其次为MICA*00201/020(20.1%)和MICA*010(17.3%),频率最低的是MICA*019和MICA*031。将MICA基因在湖南汉族人群中的分布与该基因在其他人群中的分布进行比较,显示MICA基因的分布在不同人群之间存在差异,可作为中国人群的遗传标志。     

L-选择素基因多态性与冠状动脉粥样硬化性心脏病易感性的相关性研究

目的探讨L-选择素基因P213S多态性是否与冠状动脉粥样硬化性心脏病有关联。方法采用病例-对照研究，对212例经冠状动脉造影确诊的冠心病患者和230名正常对照者进行研究。应用聚合酶链反应限制性片段长度多态性（polymemse chain reaction-restriction fragment length polymorphism，PCRRFLP）技术测定L-选择素基因多态性。结果冠心病组213P等位基因频率明显高于对照组（77．59％vs69．35％，P=0．006）。PP纯合子患冠心病的风险是SS纯合子的2．70倍（95％CI：1．07～6．81），且经Logistic回归分析校正性别、年龄、体重指数、血清总胆固醇、甘油三酯、高密度脂蛋白-胆固醇和低密度脂蛋白-胆固醇等相关因素之后，差异仍具有统计学意义。根据冠状动脉造影结果进一步对冠心病患者进行分组后分析，发现L-广选择素基因P213S多态性与病变血管支数及疾病程度无相关性。结论L-广选择素213P等位基因可能与我国汉族人冠心病的易感性相关联。     

CYP19基因多态性与子宫内膜异位症相关性的研究

目的 探讨CYP19基因多态性与中国河北省汉族育龄妇女Ⅲ、Ⅳ期子宫内膜异位症发病风险的关系.方法 采用聚合酶链反应限制性片段长度多态性方法检测102例Ⅲ、Ⅳ期子宫内膜异位症患者(病例组)与100例无子宫内膜异位症病史患者(对照组)CYP19基因115T/C、240A/G、1 531 C/T位点多态性.结果 CYP19基因115T/C的3种基因型TT、TC、CC在病例组的分布为91.18%、8.82%、0,在对照组为88.00%、11.00%、1.00%.T、C等位基因在病例组和对照组中的分布为95.59%、4.41%和93.50%、6.50%.两组比较差异无统计学意义(P＞0.05).CYP19基因240A/G的3种基因型AA、AG、GG在病例组中的分布为27.45%、49.02%、23.53%,在对照组为45.00%、41.00%、14.00%.A、G等位基因在病例组和对照组中的分布为51.96%、48.04%和65.50%、34.50%.两组比较差异有统计学意义(P＜0.05).CYP19基因1531 C/T的3种基因型CC、CT、TT在病例组中的分布为41.18%、47.06%、11.76%,在对照组分别为38.00%、42.00%、20.00%,两组间差异无统计学意义(P＞0.05).C、T等位基因在病例组和对照组中的分布为64.71%、35.29%和59.00%、41.00%.两组比较差异无统计学意义.结论 CYP19基因240GG基因型可能是Ⅲ、Ⅳ期子宫内膜异位症发生的危险因素.     

Association study of MICA gene polymorphisms with rheumatoid arthritis susceptibility in south Tunisian population

The aim of this study was to investigate the role of major histocompatibility complex (MHC) class I chain‐related gene A (MICA) polymorphisms, important in natural killer (NK) cell function, in patients with rheumatoid arthritis (RA). A transmembrane (TM) alanine‐encoding GCT repeats, termed A4, A5, A5.1, A6 and A9 in the MICA gene, and single‐nucleotide polymorphisms (SNPs): the Met129Val polymorphism (rs1051792) and the nonsynonymously coding SNP (rs1051794) were genotyped in 142 patients with RA and 123 unrelated healthy individuals using, respectively, PCR fluorescent method, nested PCR‐RFLP and allele specific PCR (ASP). Association was assessed based on the χ2 test, genotype relative risk (GRR) and odds ratio (OR) with 95% confidence intervals (CIs). Our results show a trend of association of the different MICA genotypes G/G, G/A and A/A (P = 0.029) which did not attain the significance after Bonferroni's correction (p_c = 0.08). Although, we revealed a significant association of the genotype A/A of MICA‐250 in patients with RA compared to healthy controls (pc = 0.033). In contrast, no significant differences between alleles and genotypes frequencies were found either with MICA‐TM or MICA met129 val (P > 0.05) in our sample. Moreover, stratification of patients with RA according to clinical and immunological data for the different polymorphisms studied shows a significant association of both MICA‐250 G allele (pc = 0.0075) and MICA‐250 GG genotype (pc = 0.008) and both allelic (val) (pc = 0.021) and genotypic (val/val) distribution (p_c = 0.0095) for MICA met129 val in the RF‐positive subgroup compared to RF‐negative patients with RA. In contrast, we found a strong association of the MICA‐TM A9 allele in RF‐negative patients with RA (p_c = 0.0003). This study indicates the involvement of the MICA‐250 polymorphism in the genetic susceptibility and severity to RA and suggests that variations in MICA‐TM and MICA met129 val may have an effect on RA severity in our south Tunisian sample.     

PD-1基因多态性与肺结核易感性的关系

目的探讨PD-1基因多态性与肺结核发病风险以及临床特征的相关性。方法采用PCRRFLP分析方法,检测262例肺结核患者和255例健康志愿者基因组DNA中PD-1基因SNP位点rs2227981和rs2227982基因型和等位基因频率的分布情况,分析PD-1基因多态性与肺结核易感性的关系;并收集了肺结核患者的临床资料,考察PD-1基因多态性与肺结核临床特征的相关性。结果对照组rs2227981和rs2227982基因型和等位基因频率的分布符合Hardy-Weinberg遗传平衡定律;rs2227981位点T等位基因(OR=2.721,95%CI:2.003~3.697,0.001)、rs2227982位点C等位基因(OR=1.614,95%CI:1.262~2.064,0.001)均与肺结核易感性相关;与rs2227981 CC基因型相比,携带PD-1 rs2227981 CT或TT基因型者具有更高的肺结核发病风险(OR=2.937,95%CI:2.018~4.274,0.001),且患者病灶范围较大(=0.009),痰菌阳性率较高(0.001);与rs2227982 TT基因型相比,携带rs2227982 TC或CC基因型者具有更高的肺结核发病风险(OR=1.706,95%CI:1.187~2.452,=0.004),且患者结核空洞的发生率较高(=0.021)。结论 PD-1基因rs2227981和rs2227982位点SNP多态性与肺结核易感性及临床特征相关。     

Association of CD22 gene polymorphism with susceptibility to limited cutaneous systemic sclerosis

Activating and inhibitory signal transducers, CD19 and CD22, have been substantially implicated both in human systemic sclerosis (SSc) and tight-skin mouse, a model for SSc. We previously showed that a single nucleotide polymorphism (SNP) in CD19 promoter region was significantly associated with increased CD19 expression level and with susceptibility to SSc. In the present study, we examined whether CD22 polymorphisms were associated with susceptibility to SSc. CD22 variations were genotyped in 126 Japanese patients with SSc [47 diffuse cutaneous SSc and 79 limited cutaneous SSc (lcSSc)] and 93 unrelated healthy controls. At the c.2304C > A SNP coding for a synonymous substitution in exon 13, A/A genotype was observed in six patients with SSc (4.8 %) but none in the controls (P=0.040). All six patients with A/A genotype belonged to the lcSSc subgroup (7.6%, P=0.008 vs controls). Surface expression level of CD22 tended to be lower in B cells from the patients with A/A genotype (n=5) as compared with C/A (n=7) or C/C (n=14) genotype (17% decrease, P=0.0032). Taken together with our previous observation on CD19 polymorphism, intrinsic difference in the expression level of CD19 and CD22 was suggested to play a causative role in a proportion of patients with lcSSc.     

CYP1B1基因多态性与子宫内膜异位症易感性的相关研究

目的 研究CYP1B1基因第2外显子119(G-T)、第3外显子432(C-G)多态性与子宫内膜异位症(endometriosis,Ems)易感性的关系.方法 采用等位基因特异性聚合酶链反应对55例Ems患者和45例对照组进行CYP1B1基因第2外显子119(G-T)、第3外显子432(C-G)突变分析,探讨Ems的发生与CYP1B1基因多态性之间的相关性.结果 CYP1B1基因密码子119中等位基因G、T在Ems组和对照组分布的差异有统计学意义(P＜0.05),其中等位基因T使Ems发病风险提高2.061倍;CYP1B1基因密码子119G/T各基因型分布两组间差异有统计学意义(P＜0.05),纯合突变(T/T)基因型、杂合突变(G/T)基因型与野生型(G/G)基因型相比,患Ems的危险度分别为2.625倍和3.214倍.以CYP1B1联合野生型GG和CC个体的OR值为1相比,CYP1B基因密码子119杂合型突变(Ala/Ser)合并密码子432野生型个体的OR值为2.976,95%CI:1.129～7.848,P＜0.05.结论 CYP1B1基因第2外显子119(G-T)突变等位基因与Ems的发生有一定关系,突变基因型增加了Ems的发病风险;CYP1B1基因第2外显子杂合型突变(Ala/Ser)联合密码子432野生型能增加Ems的发病风险.     

Further polymorphism of the MICA gene

The MHC class I chain‐related (MIC) gene family constitutes an interesting genetic group that is related to major histocompatibility complex (MHC) class I genes and is located within the MHC. The MIC gene products, MICA and MICB, have similar structures to HLA class I molecules. So far over 50 MICA alleles have been reported, which suggests that this genetic system is highly polymorphic. In order to investigate further the extent of MICA polymorphism we have studied exons 2–5 of the MICA gene in over 200 homozygous and heterozygous cell lines. Altogether we have identified 11 new MICA alleles and report 13 new nucleotide variations, one in exon 2, four in exon 3, four in exon 4, two in intron 1, one in intron 4 and one (a deletion) in exon 4. Eight of the 10 exonic variations are non‐synonymous. The deletion in exon 4 leads to a frame‐shift mutation and the introduction of a repeat of 12 leucine residues encoded by the microsatellite in exon 5. This study provides further evidence that the MICA gene is highly polymorphic. In contrast to MHC class I molecules, the polymorphic sites in MICA are predominantly within the α₂ and α₃ domains. The distribution of synonymous and non‐synonymous substitutions suggests that there is selection for the polymorphic positions, which therefore define potential functional sites in the protein. We were also able to determine the association between MICA and HLA‐B alleles in a number of homozygous cell lines bearing extended haplotypes.     

Association between angiotensin I-converting enzyme gene polymorphism and susceptibility to cancer: a meta analysis

Background: Angiotensin I-converting enzyme (ACE) gene plays an important role in the pathogenesis of cancers. The association between ACE insertion/deletion (I/D) polymorphism and the risk of various cancers has been studied. However, the results of these studies remain conflicting. Therefore, we performed a meta-analysis to evaluate the association between ACE I/D polymorphism and the risk of cancers. Methods: PubMed, Embase, ScienceDirect, Springer, CNKI, Wanfang, Weipu, CBM databases and Google Scholar were searched for case-control studies on ACE I/D polymorphism and the risk of cancers, published up to Dec 31, 2013. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of the association between ACE I/D polymorphism and cancer risk. Results: Thirty-five published studies with 5007 cases and 8173 controls were included. Overall, there were no significant association between ACE I/D polymorphism and the risk of cancers (II vs. ID+DD OR = 1.05, 95% CI = 0.89-1.23, I vs. D OR = 1.00, 95% CI = 0.89-1.13). However, when stratified by ethnicity, we found a significant association between this polymorphism and cancer risk in Caucasians (II vs. ID+DD: OR = 1.43, 95% CI = 1.02-2.00, I vs. D: OR = 1.23, 95% CI 1.01-1.49). Conclusion: ACE I/D polymorphism is associated with the cancer risk in Caucasians.     

Association of MICA polymorphism with rheumatoid arthritis patients in Koreans

To investigate whether genetic variations of MICA are associated with susceptibility to rheumatoid arthritis (RA), the (GCT)n microsatellite polymorphism of the transmembrane domain was analyzed in 144 Korean patients with RA and in 297 unrelated healthy controls. The allele frequency of MICA*A9 significantly decreased in RA patients compared with controls (9.0% vs. 15.3%, odds ratio [OR] = 0.55, p = 0.0098, p_c = 0.049), whereas the frequency of the MICA*A4 and MICA*A5.1 alleles tended to increase in RA patients (21.2% vs. 14.8%, OR = 1.55, p = 0.018, p_c > 0.05; 20.5% vs. 15.0%, OR = 1.46, p = 0.0403, p_c > 0.05). By subgroup analysis, the MICA*A4 allele significantly increased in seropositive RA patients versus controls (23.0% vs. 14.8%, OR = 1.69, p = 0.0082, p_c = 0.041). HLA-DRB1*0405 was strongly associated with RA (p_c = 0.0000008), and strong linkage disequilibrium was observed between HLA-DRB1*0405 and MICA*A4 alleles in controls (p_c = 0.000004) as well as in RA patients (p_c = 0.0012). In Korean patients, HLA-DRB1*0405 was primarily associated with RA and the weak association of RA with MICA*A4 was secondary to that with HLA-DRB1*0405. Additionally, MICA*A9 might have a weak protective effect on the susceptibility to RA in Koreans.