中国人红细胞补体受体1(CD35)分子量多态性

CR1即补体受体1型,是补体成分C3b、iC3b与C4b的受体,存在于多种细胞表面.每个红细胞表面平均有500个CR1分子,由于红细胞数量较多,所以血液中CR1大部分存在于红细胞表面[1].红细胞CR1参与多种免疫功能如调理免疫复合物[2]等,同时还发现与许多疾病有关,且与其数量或分子量多态性直接相关.目前大部分研究集中在CR1活性及数量多态性上,本研究旨在了解中国人CR1/E分子量多态性.     

红细胞补体受体1(CR1)数量基因多态性与反复呼吸道感染易感性的研究

目的通过研究红细胞补体受体1(CR1)数量基因多态性与反复呼吸道感染的相关性,探讨反复呼吸道感染(RRTI)患儿的遗传易感因素.方法利用限制性内切酶HindⅢ,聚合酶链反应限制性片段长度多态性(PCR-RFLP)分析,基因测序等技术测定58例RRTI患儿(病例组)和56例正常儿童(对照组)的红细胞CR1数量基因多态性,并进行比较.结果病例组中CR1基因HH、HL和LL基因型分布频率分别为34.2%、55.3%和10.5%,而对照组中HH、HL和LL基因型分布频率分别为75%、21.4%和3.6%.两组CR1基因型的分布频率差异有显著性(P＜0.001).病例组中HL和LL基因型占优势(OR=5.77).两组CR1基因等位基因的分布频率差异也有显著性(P＜0.01),病例组中L等位基因分布频率高于对照组.结论红细胞补体受体1(CR1)数量基因多态性与反复呼吸道感染有相关性,提示CR1基因HindⅢ酶切位点多态性可能在决定个体反复呼吸道感染遗传易感性方面有重要作用.     

ATM基因rs227060位点单核苷酸多态性与肺癌易感性的相关性

目的:探讨共济失调毛细血管扩张症突变基因(ataxia telangiectasia mutated,ATM)rs227060位点单核苷酸多态性(single nucleotide polymorphisms,SNPs)与肺癌易感性之间的相关性.方法:采用聚合酶链反应-SNP敏感性分子开关方法,检测225例肺癌患者和128例健康体检者ATM基因rs227060多态位点等位基因以及基因型频率分布特点;并应用非条件Logistic回归法统计分析rs227060单核苷酸多态性与肺癌的相关性.结果:rs227060多态位点共检测出CC,CT,TT三种基因型和C,T两种等位基因,其在肺癌组与对照组的基因型分布频率为:CC基因型17.3％与29.7％、CT基因型61,4％与59.3％、TT基因型21.3％与11％,两组间基因型频率和等位基因频率分布差异均有统计学意义(P＜0.05).在对ATM rs227060基因型的多态性分析过程中发现:吸烟史在肺癌组与对照组相比差异无统计学意义(P＞0.05),而年龄、性别、肿瘤家族史在肺癌组与对照组相比差异均有统计学意义(P＜0.05);且以CC基因型作为对照,携带TT基因型的个体患肺癌的风险是携带CT基因型个体的3.49倍(OR=1.829;95％CI:1.045～3.199).结论:ATM基因rs227060位点单核苷酸多态性与肺癌易感性存在相关性,且携带TT基因型可增加肺癌的发病风险.     

山东地区汉族人 HLA-DPB1基因单核苷酸多态性

使用第十一届国际组织相容性会议提供的HLA－DPB1引物序列，由PCR技术扩增人HLA－DPB1基因第二外显子。产物纯化后，直接核酸序列分析确定个体的HLA－DPB1外显子核酸序列。使用基因定型软件与国际上公布的HLA－DPB1核酸序列构建的基因型核酸序列数据库进行比较，确定个体的基因型别、确定等位基因类型。研究结果提示中国人HLA－DPB1第二外显子基因序列与国际上公布的序列基本一致，但有不同之处，多处存在单核苷酸多态性（SNP），提示存在有新的等位基因。对51例个体研究显示，出现频率最高的等位基因是DPB1＊02012。     

肿瘤患者红细胞CR1分子数量及基因多态性的变化

我们建立的红细胞ＣＲ1分子酶联定量测定法 ,具有良好的灵敏性和重复性[1] ,用此种方法测定自身免疫疾病 ,与国外报道的结果完全相同[2 ] 。最近对良、恶性肿瘤患者红细胞ＣＲ1分子的数量表达Ａ4 0 5值进行测定发现 ,恶性肿瘤患者红细胞ＣＲ1分子数量表达较良性肿瘤患者和正常人群都明显下降 ,并且是后天获得性。此点国外尚无报道。本文对良、恶性肿瘤患者红细胞ＣＲ1分子的数量及其基因多态性表达变化进行了研究 ,报告如下。1　材料与方法1.1　病例来源及血标本　 10 2例肝癌患者系第二军医大学附属东方肝胆医院住院确诊病人 ;大肠癌2 6例…     

反复呼吸道感染患儿红细胞CR1数量基因多态性及其红细胞免疫功能

目的 通过研究红细胞补体受体1（CR1）数量基因多态性与红细胞免疫功能的相关性,探讨反复呼吸道感染（RRTI）患儿的遗传易感因素。方法 采用红细胞C3b受体花环率和红细胞免疫复合物花环率,并利用限制性内切酶Hind Ⅲ,聚合酶链反应（PCR）测定38例RRTI患儿（病例组）和56例正常儿童（对照组）的红细胞CR1活性与CR1数量基因多态性,并进行比较。结果 病例组中红细胞C3b受体花环率明显低于正常对照组,差异有显著性（P〈0．01）,而红细胞免疫复合物花环率略低于正常对照组,差异无显著性（P〉0．05）,且CR1基因HH、HL和LL基因型分布频率分别为34．2％、55．3％和10．5％,而对照组中H14、HL和LL基因型分布频率分别为75％、21．4％和3．6％。两组CR1基因型的分布频率差异有显著性（P〈0．01）。病例组中肌和LL基因型占优势（OR：5．77）。两组CR1基因等位基因的分布频率差异也有显著性（P〈0．01）,病例组中L等位基因分布频率高于对照组。结论 反复呼吸道感染患儿CR1数量基因多态性与红细胞免疫功能有相关性,提示CR1基因Hind Ⅲ酶切位点多态性可能在决定个体反复呼吸道感染遗传易感性方面有重要作用。     

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.     

中国人膜联蛋白A1基因单核苷酸多态性及其与2型糖尿病的相关性

目的　筛查上海地区汉族人群中膜联蛋白 A1(annexin A1,ANXA1)基因的单核苷酸多态性 (single nucleotide polymorphisms,SNPs) ,并通过关联分析研究其与 2型糖尿病的相关性。方法　选取2 4例 2型糖尿病患者的 DNA样本 ,采用直接测序法对 ANXA1基因的启动子区、全部外显子及其临近内含子区作 SNPs筛查 ,并在其余的 171例 2型糖尿病和 189名正常对照间作进一步的基因分型。结果ANXA1基因测序长度 6 798bp,共检出 7个 SNPs,其中启动子区 2个 (- 7974 C>T,- 70 4 0 G>T) ,内含子区 3个 ( 90 5 9A>G, 92 0 4 C>T, 10 4 86 A>G) ,5′-非翻译区 1个 (- 6 6 14 A>G) ,编码区 1个( 1784 A>G)。进一步的基因分型后显示这些 SNPs的等位基因频率在 2型糖尿病和正常对照组之间差异无显著性 (P>0 .0 5 )。结论　ANXA1基因多态性与上海地区汉族人群中 2型糖尿病无显著相关性。     

PATZ1基因单核苷酸多态性与无精症的关系

目的 研究PATZ1基因的4个单核苷酸多态性(single nucleotide polymorphism,SNP)rs2240424、rs2057951、rs2240427和rs714909的多态性与无精症的关系.方法 用PCR-限制性片段长度多态性分析方法,在180例无精症患者和190名正常男性中对上述4个SNP位点的基因频率和基因型频率分布进行调查.结果 rs2057951位点的等位基因C(35.0%vs.27.6%,P=0.031)和带有等位基因C个体(CT+CC)(57.8%vs.46.3%,P=0.027)的频率在无精症患者显著高于正常男性.4种SNP的单倍型在两组人群中的分布差异有统计学意义(P=0.01),单倍型ACAC(11.1%vs.6.6%,P=0.029)和ACGC(11.2%vs.5.2%,P=0.003)在无精症患者中显著高于正常男性.结论 PTAZ1的rs2057951位点的等位基因C和单倍型ACAC和ACGC增加无精症的易感性,提示PTAZ1基因可能与无精症发病相关.     

肝病患者外周血红细胞表面CR1的表达水平及其意义

许多研究表明，肝病的发生发展与机体免疫功能的紊乱具有密切关系。为了探讨不同肝病患者的免疫功能状况，我们采用ELISA法，检测了86例急性肝炎、慢性肝炎、肝硬化及原发性肝癌患者外周血红细胞上1型补体受体(CR1)的表达水平，并分析了其临床意义。     

Association of the Single-Nucleotide Polymorphism and Haplotype of the Complement Receptor 1 Gene with Malaria

PurposeAlthough the polymorphisms of erythrocyte complement receptor type 1 (CR1) in patients with malaria have been extensively studied, a question of whether the polymorphisms of CR1 are associated with severe malaria remains controversial. Furthermore, no study has examined the association of CR1 polymorphisms with malaria in Chinese population. Therefore, we investigated the relationship of CR1 gene polymorphism and malaria in Chinese population.ResultsThere were no significant differences in the genotype, allele and haplotype frequencies of CR1 gene rs2274567 G/A, rs4844600 G/A, and rs2296160 C/T polymorphisms between patients with malaria and controls. Furthermore, there was no association of polymorphisms in the CR1 gene with the severity of malaria in Chinese population.ConclusionThese findings suggest that CR1 gene rs2274567 G/A, rs4844600 G/A, and rs2296160 C/T polymorphisms may not be involved in susceptibility to malaria in Chinese population.     

BARD1单核苷酸多态性与汉族儿童神经母细胞瘤相关性的研究

目的 探讨BARD1单核苷酸多态性与汉族儿童神经母细胞瘤的相关性.方法 采用病例对照研究,收集242例汉族神经母细胞瘤患儿及301例汉族健康儿童的外周血,通过PCR方法扩增目的DNA,应用Sequenom massarray对所扩增的DNA进行基因分型.以x2检验及logistics分析比较不同组基因型与神经母细胞瘤的关系.结果 BARD1的21个标签SNPs位点均符合Hardy-Weinberg平衡,BARD1的21个SNPs等位基因频率在患者组与对照组之间差异均无统计学意义(P＞0.05).结论 未发现BARD1单核苷酸多态性与汉族儿童神经母细胞瘤有相关性.     

精神分裂症与NOS1多态性的关联研究

目的 探讨一氧化氮合酶1(nitric oxide synthase 1,NOS1)基因多态性与精神分裂症易感性的相关性.方法 选取NOS1区域的28个标签单核苷酸多态性(single nucleotide polymorphisms,SNPs)位点,应用Illumina GoldenGate定制芯片对382例汉族精神分裂症患者和448名正常人的DNA进行分型,并分析其与精神分裂症的相关性.结果 单位点分析提示SNP位点rs1520811与精神分裂症存在关联,但是经过Bonferroni多重校正后差异无统计学意义(P＞0.05).单体型分析未发现单体型与精神分裂症的相关性.结论 未证实NOS1为精神分裂症的易感基因.     

Scavenger Receptor Class B Type 1 Gene rs5888 Single Nucleotide Polymorphism and the Risk of Coronary Artery Disease and Ischemic Stroke: A Case-Control Study

Background: Our previous studies have showed that the rs5888 single nucleotide polymorphism (SNP) in Scavenger receptor class B type 1 (SCARB1) gene is associated with serum lipid levels in the general Chinese populations. The present study was undertaken to detect the associations between rs5888 SNP and the risk of coronary artery disease (CAD) and ischemic stroke (IS).Methods: A total of 1,716 unrelated subjects (CAD, 601; IS, 533; and healthy controls, 582) were included in this study. Genotyping of the rs5888 SNP were determined by polymerase chain reaction and restriction fragment length polymorphism.Results: The genotypic frequencies of SCARB1 rs5888 SNP were different between CAD patients and controls, the subjects with TT genotype had high risk of CAD (OR = 1.76, P = 0.038 for TT vs. CC; and OR = 1.75, P = 0.036 for TT vs. CC/CT). There was no significant association between genotypes and the risk of IS. Further analysis showed that the subjects with TT genotype in the total population had lower levels of high-density lipoprotein cholesterol than the subjects with CC/CT genotypes (P < 0.05), the subjects with TT genotype in controls but not in CAD or IS patients had higher levels of serum LDL-C and ApoB than those with CC genotype (P < 0.05 for each).Conclusions: The present study suggests that the SCARB1 rs5888 SNP influences serum lipid levels, and is associated with the risk of CAD.     

Common Polymorphisms in the CACNA1H Gene Associated with Childhood Absence Epilepsy in Chinese Han Population

Variants with a relatively high frequency in the CACNA1H gene have previously been identified in cases of childhood absence epilepsy (CAE) in the Chinese Han population most of which are located in exons 6 to 12. In present study we attempted to further investigate whether the CACNA1H gene is associated with CAE. Exons 6 to 12 of CACNA1H gene were sequenced in samples of 100 CAE trios recruited consecutively, and 191 normal human controls. Single nucleotide polymorphisms (SNPs) were studied in both single locus and haplotype analyses in 218 CAE trios, of which 118 trios were selected from our previous research. Case-control comparisons and the transmission disequilibrium test (TDT) both supported a coding SNP (cSNP) rs9934839 (R603R) in exon 9 as being close related to CAE. The carriers of the G allele of rs9934839 had a 3-fold higher risk of CAE than non-carriers. Moreover, another cSNP rs8044363 was predicted to be connected directly with CAE in a Bayesian network. In addition, two haplotypes consisting of five cSNPs in the region of CACNA1H were statistically associated with CAE. Our research provides new evidence to further support the hypothesis that CACNA1H may be an important susceptibility gene for CAE in the Chinese Han population.     

Meta-Analysis of the Association of the Rs2234693 and Rs9340799 Polymorphisms of Estrogen Receptor Alpha Gene with Coronary Heart Disease Risk in Chinese Han Population

Objective: The association between a common variant of the ESR1 gene rs2234693 and rs9340799 polymorphisms with coronary heart disease (CHD) have been reported, but the available data on this relationship are inconsistent. A meta-analysis was performed to quantitative analysis the association of ESR1 gene polymorphisms and CHD risk using previous case-control studies in Chinese Han population.Methods: Several electronic databases were searched for relevant articles up to August 2012. After data collection, a meta-analysis was performed to assess heterogeneity, combine results and evaluate variations. Different effect models were used according to the difference in heterogeneity. Sensitivity analysis was assessed by omitting one study at a time. Publication bias was examined using Begg''s funnel plot and Egger''s linear regression test.Results: Ten studies covering 3400 subjects on rs2234693 and rs9340799 polymorphisms in the ESR1 gene with CHD risk was included in this meta-analysis. For rs2234693 polymorphism, ten studies were combined to the meta-analysis. A significantly increased CHD risk was found in a dominant model (OR=1.35, 955 CI=1.01-1.81, P=0.05), recessive model (OR=1.40, 95% CI=1.15-1.69, P=0.0007), and additive model (OR=1.67, 95% CI=1.19-2.34, P=0.003). Subgroup for male but not for female showed that the CC genotype could increase the risk of CHD compared with TT and TC genotype in Chinese Han population. Concerning rs9340799 polymorphism, eight studies were combined to the meta-analysis. And no evidence of significant association with CHD risk was found in all genetic models.Conclusion: Our meta-analysis of 10 studies involving Chinese Han population suggests that the CC genotype of the ESR1 rs2234693 polymorphism is significantly associated with an increased risk of CHD in males only. There was no evidence however, of a significant association between the ESR1 rs9340799 polymorphism and CHD risk.     

Interleukin-13 Receptor A1 Gene Polymorphism and IL-13 Serum Level in Atopic and Non-atopic Egyptian Children

Objectives: To assess serum interleukin (IL) 13 levels in atopic diseases and to determine the role of IL-13R A₁ gene polymorphism (+1398 A/G) in pathogenesis of these diseases. Methods: Serum total immunoglobulin (Ig) E and IL-13 levels were measured by ELISA and the IL-13R A₁ gene (+1398 A/G) was screened by PCR-restriction fragment length polymorphism (RFLP) in 240 asthmatic children (120 atopic and 120 nonatopic) and 120 allergic rhinitis patients compared with 120 age-matched controls. Results: No significant association was observed between genotype frequencies of the IL-13R A₁ +1398 A/G polymorphism in patients groups compared to in controls. There was a significant increase in serum levels of total IgE & IL-13 towards heterozygous AG and homozygous GG than homozygous AA in atopic asthma, non-atopic asthma and allergic rhinitis groups (P < 0.001 for each). A highly significant increase of serum IL-13 in atopic asthma as compared with controls (P < 0.001) and with nonatopic asthmatics (P < 0.001) was shown. Conclusion: The IL-13R A₁ +1398 A/G polymorphism does not contribute to asthma or allergic rhinitis susceptibility, yet serum IL-13 can be used as a marker in atopic diseases and to differentiate between atopic and non-atopic asthma.     

HLA-DQB1基因多态性与中国汉族人群系统性红斑狼疮的相关性

目的 探讨HLA-DQB1基因单核苷酸多态性(single nucleotide polymorphisms,SNP)与汉族人群系统性红斑狼疮(systemic lupus erthematosus,SLE)遗传易感性的相关性.方法 通过聚合酶链式反应-连接酶检测反应(polymerase chain reaction-ligase detection reaction,PCR-LDR)技术对908例SLE患者和961例健康对照rs3129716(HLA-DQB1)位点进行基因分型,同时结合临床表现分型,分析该位点与疾病及临床表型的相关性.分型结果用PLINK1.07软件进行统计分析.结果 rs3129716(HLA-DQB1)位点等位基因频率和基因型频率在SLE疾病组和对照组的分布差异无统计学意义(P＞0.05).三种遗传模型下的分析显示,两组间差异无统计学意义(P＞0.05).将SLE患者按血清学指标及临床表现分型,未发现相关性.结论 rs3129716(HLA-DQB1)与中国汉族人群SLE患者遗传易感性不相关.     

ETS1基因与中国北方汉族人群系统性红斑狼疮的相关性研究

目的 验证ETS1基因在北方汉族人群系统性红斑狼疮(systemic lupus erythematosus,SLE)发生中的作用.方法 应用病例-对照关联研究,在山东汉族人群中收集231例SLE患者和474名正常对照,采用Taqman探针对ETS1基因3’非翻译区区域单核苷酸多态位点rs1128334与rs4937333进行基因分型,并对数据进行统计学计算和单倍型分析.结果 rs1128334等位基因A在病例组中的频率显著高于对照组(42.8％ vs.29.1％,OR=1.824,95％CI:1.445～2.302,P＜0.01),rs4937333等位基因T在病例组中的频率显著高于对照组,差异具有统计学意义(47.6％ vs.38.1％,OR=1.478,95％CI:1.181～1.851,P＜0.01).两位点的单倍型分析显示单倍型A-T与SLE的发病风险显著相关(P＜0.05,OR=0.738,95％CI:0.564～0.964),而单倍型G-C可以显著降低SLE的发病风险(P＜0.01,OR=0.296,95％CI:0.232～0.378).结论 ETS1基因rs1128334和rs4937333位点与北方汉族人群系统性红斑狼疮相关.     

血管紧张素原、血管紧张素Ⅱ一型受体基因多态性与原发性高血压的相关性研究

目的 :探讨血管紧张素原AGT(M2 3 5T)、血管紧张素Ⅱ一型受体AT1 R(A1166C)基因多态性与中国四川籍人群原发性高血压(EH)的关系。方法 :采用聚合酶链反应 (PCR)及限制性片段长度多态性分析 (RFLP)方法分析人类白细胞染色体DNA中AGT、AT1 R基因多态性。结果 :12 2例EH病例组与 87例正常对照组AGT等位基因频率T、M分别为 :T :0 .82 8vs 0 .661,M :0 .172vs 0 .3 3 9。AT1 R等位基因频率A、C分别为 :A :0 .968vs 0 .989,C :0 .0 3 2vs 0 .0 11。各基因型频率及等位基因频率符合Hardy Weinberg平衡定律。EH病例组AGT基因T等位基因频率和TT型明显高于对照组(χ2 =11.7,P <0 .0 1和 χ2 =15 .6,P <0 .0 1)。结论 :AGT基因多态性与EH密切相关 ;而AT1 R基因多态性与EH无关。