慢性阻塞性肺病TNFA和LTA基因等位基因变异分析

目的中国北方汉族人群中研究TNF超家族基因等位基因变异是否与慢性阻塞性肺病(COPD)相关联.方法 以50例COPD患者为研究对象,应用聚合酶链反应-限制性片段长度多态性方法研究TNF超家族基因(TNFA和LTA)等位基因变异分布.结果 TNFA基因多态性位点-308G/A COPD组和对照组比较AA基因型频率分布差异显著(χ2=7.111,P＜0.01),OR值为10.756(95%CI为9.875～12.640).-308G/A多态性位点A等位基因频率差异显著(χ2=8.219,P＜0.01);LTA基因 252A/G多态性位点AG基因型频率分布COPD组与对照组比较差异显著(χ2=11.974,P＜0.01),OR值为4.373(95%CI为3.301～6.872).LTA基因 252 A/G多态性位点G等位基因频率差异不显著.在COPD患者组中TNFA基因GG正常基因型和LTA基因AG杂合基因型结合个体频率比对照组显著增高(χ2=4.10,P＜0.05).结论 中国北方汉族人群LTA基因等位基因变异、TNFA基因多态性变异组合与COPD相关联.     

survivin单核苷酸多态性与膀胱癌易感性的关系探讨

目的探讨中国汉族人群survivin基因多态性与膀胱癌易感性的关系。方法采用聚合酶链反应—限制性片段长度多态技术(PCR-RFLP)检测115例膀胱癌患者和166例健康人survivin基因启动子区域的C-31G、第4外显子的A9194G单核苷酸多态性,分析其与膀胱癌易感性的关系。结果 C-31G位点的GG基因型相对于CC基因型,明显减少了患膀胱癌的风险(OR=0.47,P<0.05);A9194G位点的等位基因G相对于等位基因A,显著减少患膀胱癌病的风险(OR=0.65,P<0.05)。G-G单倍体相对于C-A单倍体,显著降低患膀胱癌的风险(OR=0.17,P<0.01)。结论 survivin基因与中国汉族人群膀胱癌易感性密切相关,C-31G、A9194G两位点的多态性在膀胱癌易感性中存在协同作用。     

IL-12RB2 rs3790567A/G位点单核苷酸多态性与原发性胆汁性肝硬化易感性的Meta分析

目的评价IL-12RB2 rs3790567A/G位点单核苷酸多态性与原发性胆汁性肝硬化(primary biliary cirrhosis,PBC)易感性的关系。方法通过计算机检索Pub Med、Embase、the Cochrane Library、Web of Science、中国知网、万方等中英文数据库,检索IL-12RB2 rs3790567A/G位点单核苷酸多态性与PBC相关的病例-对照研究。以PBC组与对照组人群基因型频率的OR值和95%CI为效应指标,采用随机或固定效应模型进行定量合并分析,并进行偏倚评估和敏感性分析。采用Rev Man 5. 3软件进行Meta分析。结果本研究共纳入文献6篇,PBC组(病例组) 1 584例,健康对照组2 648名。Meta分析结果表明,IL-12RB2 rs3790567A/G位点与PBC发病因素密切相关。5个基因型结果如下:显性模型:AA+AG vs GG,OR=1. 20,95%CI:1. 11～1. 29,差异有统计学意义(P 0. 05);隐性模型:AA vs AG+GG,OR=1. 59,95%CI:1. 25～2. 02,差异有统计学意义(P 0. 05);共显性模型:AG vs AA,OR=0. 83,95%CI:0. 53～1. 32,差异有统计学意义(P 0. 05); GG vs AA,OR=0. 03,95%CI:0～0. 07,差异有统计学意义(P 0. 05);等位基因模型A vs G,OR=1. 02,95%CI:0. 72～1. 45,差异无统计学意义(P 0. 05)。以研究地理位置及种族不同进行亚组分析,亚洲人显性基因模型:AA+AG vs GG,OR=1. 17,95%CI:0. 89～1. 55,差异无统计学意义(P=0. 26)。高加索人显性基因模型:AA+AG vs GG,OR=1. 30,95%CI:1. 17～1. 44,差异有统计学意义(P 0. 05);亚洲人隐性基因模型AA vs AG+GG,OR=1. 39,95%CI:1. 01～1. 91,差异无统计学意义(P=0. 05)。高加索人隐性基因模型:AA vs AG+GG,OR=1. 94,95%CI:1. 34～2. 81,差异有统计学意义(P 0. 05);亚洲人等位基因模型A vs G:OR=1. 26,95%CI:0. 70～2. 26,P 0. 05,高加索人A vs G,OR=1. 02,95%CI:0. 72～1. 45,差异无统计学意义(P 0. 05)。结论 IL-12RB2 rs3790567A/G在PBC AA和AA+AG基因模型中易感性显著增加,且通过亚组分析,证明种族间差异有统计学意义。     

岩藻糖基转移酶2基因多态性与炎症性肠病易感性Meta分析

目的探讨岩藻糖基转移酶2(fucosyltransferase 2,FUT2)在A385T位点和G428A位点的基因多态性与炎症性肠病(inflammatory bowel disease,IBD)易感性的关系.方法计算机检索EMBASE、PubMed、EBM Reviews、Ovid、Springer、中国期刊全文数据库(CNKI)、万方数字化期刊全文数据库,查找关于FUT2基因多态性与IBD相关性的研究,对纳入文献进行质量评价,提取有效数据,使用Review Manager 5.3和Stata 12.0软件进行Meta分析,并用Begg's漏斗图进行发表偏倚检测.结果共纳入10篇文献,病例组3682例,对照组5470例.各种遗传模型在溃疡性结肠炎(ulcerative colitis,UC)中,显性遗传模型[(AA+AT)vs TT]中OR=1.00(95%CI:0.83-1.21),[(GG+GA)vs AA]中OR=1.05(95%CI:0.81-1.36);隐性遗传模型[(AT+TT)vs AA]中OR=0.96(95%CI:0.73-1.25),[(GA+AA)vs GG]中OR=0.70(95%CI:0.36-1.36);共显性遗传模型中(AA vs TT)中OR=1.02(95%CI:0.82-1.27),(GG vs AA)中OR=1.23(95%CI:0.93-1.63);等位基因模型(A vs T)中OR=1.06(95%CI:0.95-1.17),(G vs A)中OR=1.18(95%CI:0.68-2.04).各种遗传模型在克罗恩病(Crohn's disease,CD)中,显性遗传模型[(AA+AT)vs TT]中OR=0.60(95%CI:0.43-0.85),[(GG+GA)vs AA]中OR=0.51(95%CI:0.38-0.70);隐性遗传模型[(AT+TT)vs AA]中OR=0.99(95%CI:0.73-1.35),[(GA+AA)vs GG]中OR=1.49(95%CI:1.17-1.91);共显性模型(AA vs TT)中OR=1.37(95%CI:0.95-1.98),(GG vs AA)中OR=0.46(95%CI:0.33-0.65);等位基因模型(G vs A)中OR=0.67(95%CI:0.57-0.79),(G vs A)中OR=0.67(95%CI:0.57-0.79).结论 FUT2 A385T与G428A基因多态性与UC易感性无关.亚洲人群中FUT2 A385T上基因型TT会增加CD的发病风险.FUT2 G428A多态性与CD相关,携带等位基因A会增加CD的易感性.     

CTLA-4+49A＞G基因多态性与上消化道肿瘤相关性的Meta分析

[目的]探讨上消化道肿瘤包括食管癌、胃癌与CTLA-4+49AG基因多态性之间的相关性。[方法]计算机检索Pubmed、Embase、Cochran、中国生物医学文献数据库、中国知网、维普及万方数据库,检索时间截止至2018-09-21,收集CTLA-4+49位点基因多态性与食管癌、胃癌相关性的病例-对照研究,依据纳入和排除标准,由2名收集者独立获取文献,提取数据并予以评价其质量。RevMan5.3、Stata12.0软件进行系统分析。[结果]8个病例-对照研究被纳入,其中3个有关食管癌,5个有关胃癌;共3 045例患者和3 545例对照者。分析结果示,当有关上消化道肿瘤的所有研究合并时:均运用随机效应模型,显性遗传模型GG+GA∶AA:两者差异无统计学意义(OR=l.15,95%CI:0.74～1.81);隐性遗传模型GG:GA+AA(OR=0.99,95%CI:0.74～1.31),共显性模型GG∶AA(OR=1.14;95%CI:0.67～1.95),GA∶AA(OR=1.20;95%CI:0.80～1.79),等位基因模型G∶A(OR=1.06;95%CI:0.82～1.38)以上结果均示CTLA-4+49AG位点基因多态性与上消化道肿瘤(包括胃癌、食管癌)易感性无相关性。有关胃癌的5项研究合并后,各遗传模型亦示CTLA-4+49AG位点基因多态性与胃癌易感性无相关性。[结论]CTLA-4+49AG位点单核苷酸多态性与上消化道肿瘤(包括胃癌、食管癌)无相关性。     

白细胞介素-8基因251 A/T位点的多态性与亚洲人群胃癌易感性的Meta分析

[目的]用Meta分析的方法评价IL-8基因251 A/T位点的多态性与亚洲人群胃癌易感性的关系。[方法]检索Web of science、PubMed、EMBASE、万方数据库、中国生物医学文献数据库、中文科技期刊数据库、中国期刊全文数据库,日期均从各数据库开始建库至2018年1月。全面检索IL-8基因251 A/T位点的多态性与胃癌易感性的病例对照研究文献,采用STATA统计软件进行Meta分析。[结果]最终纳入15篇病例对照研究进行Meta分析,共计3738例胃癌患者、4497例健康对照者。分析结果显示,IL-8基因251 A/T位点在等位基因模型(A vs T:OR=1.12;95%CI为1.04~1.21;P=0.002)、共显性模型(AA vs AT:OR=1.15;95%CI为1.00~1.32;P=0.050)、相加模型(AA vs TT:OR=1.36;95%CI为1.18~1.57;P=0.000)、相加模型(AT vs TT:OR=1.23;95%CI为1.11~1.36;P=0.000)、显性模型(AA vs AT+TT:OR=1.23;95%CI为1.08~1.40;P=0.002)、隐性模型(TT vs AA+AT:OR=1.26;95%CI为1.15~1.39)下均与亚洲人群胃癌易感性有关。[结论]IL-8基因251 A/T位点多态性与亚洲人群胃癌的易感性相关。     

抗原肽运载体基因多态性与Graves病关联性的初步探讨

目的　探讨抗原肽运载体 (TAP)基因在华南地区一组汉族人中的分布及其与Graves病的关联性。方法　采用扩增阻滞突变体系 (ARMS)检测TAP1及TAP2基因各多态性位点在 67例Graves病患者及 69例正常对照组中的分布。结果　TAP基因各多态性位点在本组华南地区健康汉族人中的分布与国内外其他组资料基本一致 ,但存在一定程度的差异 ,提示TAP1及TAP2基因可能有民族、地区分布的差异。TAP1基因的单倍体型TAP1D在正常人群中的分布频率显著高于Graves病组(RR =0 1 7,P <0 0 1 ) ,TAP1C在正常人群中的分布频率显著低于Graves病组 (RR =2 0 5 ,P <0 0 5) ;而TAP2基因的单倍体型TAP2A在正常人群中的分布频率显著高于Graves病组 (RR =0 46 ,P <0 0 5) ,TAP2F在正常人群中的分布频率显著低于Graves病组 (RR =9 95 ,P <0 0 5)。结论　TAP1D及TAP2A与Graves病的保护性相关 ,可能是Graves病的保护基因 ;TAP1C及TAP2F与Graves病的易感性相关 ,可能是Graves病的易感基因     

EDNRA和EDNRB基因单核苷酸位点多态性与缺血性脑卒中的相关性

目的探讨中国北方地区汉族人群内皮素受体(EDNR)A和EDNRB基因中单核苷酸多态性(SNP)与缺血性脑卒中(IS)的相关性。方法检测EDNRA基因的3个位点:rs1801708、rs5333、rs5335和EDNRB基因的2个位点:rs3818416、rs5351在对照组、IS组中的多态分布。结果在男性群体中,EDNRA基因rs5335位点突变纯合型CC发病危险度明显降低(P=0.016;OR=0.52;95%CI=0.31~0.88);在女性群体中,EDNRA基因rs1801708位点中,突变纯合型AA发病危险度明显高于G基因携带者(P=0.019;OR=2.65;95%CI=1.18~6.00)。结论 EDNRA基因rs5335位点的C等位基因能够降低北方汉族男性人群IS的发病风险,rs1801708位点的A等位基因能够增加北方汉族女性人群IS的发病风险。     

LMP2/LMP7基因单倍型与肠道结核感染易感的相关性研究

目的 探讨中国汉族人群中抗原递呈基因LMP2/LMP7单倍体型与肠道结核感染的遗传易感性关联.方法 提取189例肠道结核感染患者及221例健康志愿者外周全血基因组DNA,采用PCR-RFLP的方法检测两组人群中LMP2-60/LMP7-145位于基因编码区的两个多态性位点基因型;利用PHASE1.0软件构建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,并进行单倍体型与肠道结核感染易感风险关联的统计学分析.结果 LMP2-60/LMP7-145多态性在中国人群中均存在,LMP2/LMP7多态性位点各自的等位基因频率分布符合Hardy-Weinberg平衡定律;肠道结核感染患者与健康对照人群中LMP2/LMP7两个多态性位点的基因型频率没有统计学差异(P＞0.05);经校正混杂因素后,Logistic回归分析结果显示两个位点所构建的单倍体型LMP2(Cys)-LMP7 (Lys)在两组间具有统计学差异(P=0.001、OR=4.02、95％ CI 2.48 ～ 9.62).结论 在中国汉族人群中,LMP2/LMP7基因编码区两个多态位点的单倍体型与肠道结核的感染有着较强的遗传易感关联.     

PDE4D基因多态性与辽宁省汉族人群缺血性脑卒中的相关性

目的探讨磷酸二酯酶(PDE)4D基因多态性与辽宁省汉族人群缺血性脑卒中(IS)潜在的遗传发病机制分子流行病学依据。方法采用病例对照的研究方法,检测PDE4D基因多态性位点SNP83、SNP 87、SNP219和SNP220在病例组、对照组中的频率分布。结果病例组SNP83位点CC基因型和C等位基因型频率分布均高于对照组(CC:P=0.001;OR=1.788;95%CI:1.280～2.497;C:P=0.003;OR=1.368;95%CI:1.115～1.678)。SNP219位点AA基因型和A等位基因型频率高于对照组(AA:P=0.029;OR=1.444;95%CI:1.037～2.010;A:P=0.048;OR=1.228;95%CI:1.001～1.505)。经条件Logistic回归校正后,SNP83CC基因型分布频率仍然高于对照组(P=0.036;OR=1.603;95%CI:1.032～2.489),SNP219AA基因型分布频率也仍然高于对照组(P=0.046;OR=1.567;95%CI:1.008～2.436)。由SNP219、SNP220位点构建的单体型中,AA单体型频率病例组高于对照组(P=0.013;OR=1.296;95%CI:1.056～1.591)。GA单体型频率病例组低于对照组(P=0.005;OR=0.650;95%CI:0.482～0.878)。结论 PDE4D基因SNP83、SNP219位点可能与辽宁省汉族人群大血管性IS具有相关性,而在由SNP219、SNP220位点构建的单体型中,AA可能是危险性单体型,GA可能是保护性单体型。     

Association study between hypertension and A/G polymorphism at codon 637 of the transporter associated with antigen processing 1 gene.

To explore the effect of A/G polymorphisms at codon 637 of the transporter associated with antigen processing 1 (TAP1) gene on the risk of hypertension. A case-control study of epidemiology was conducted. The case group included 277 community-based patients (136 males and 141 females; mean age 58.7+/-12.1 years) diagnosed with hypertension, and the control group consisted of 227 healthy subjects (95 males and 132 females; mean age 51.29+/-12.16 years) from the same community. The A/G polymorphisms at codon 637 of the TAP1 gene was examined by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method with genomic DNA. The effect of A/G polymorphisms at codon 637 of the TAP1 gene on hypertension was analyzed by using multivariate unconditional logistic regression models. The contribution of TAP1 637 A/G allele frequencies of the control group was consistent with that predicted by the Hardy-Weinberg equilibrium test (x2=230, p=0.632). There was a significant difference in the frequency of the A/G polymorphisms at codon 637 of the TAP1 gene between hypertensive patients (74.4/25.6%) and controls (82.4%/17.6%), x2=9.324, p=0.002. Genotype model (AA-AG-GG) analysis showed that there was a significant difference in the frequency of the recessive genotype between cases and controls (AA/AG vs. GG: odds ratio [OR]=3.046, 95% confidence interval [CI]=1.138-8.153) after adjustment for the covariates of age, serum total cholesterol, triglycerides, body mass index (BMI) and smoking. But there were no significant differences in the frequency of the genotype for the dominant model (AA vs. AG/GG: p=0.293) or additive model (AA vs. AG vs. GG: p=0.081) after adjustment. One-way ANOVA analysis showed that the systolic blood pressure, diastolic blood pressure, and BMI levels of the GG genotype were significantly higher than those of the AA or AG genotypes. In conclusion, our findings suggest that the A/G polymorphisms at codon 637 of the TAP1 gene contributes to the risk of hypertension, possibly via the increases in blood pressure and BMI.     

Interleukin-17F gene polymorphisms in Korean patients with Behçet’s disease

IL-17 is a novel cytokine that is characterized by an ability to induce several types of cells to secrete proinflammatory cytokines in various inflammatory diseases. This study analyzed the influence of IL-17F gene polymorphisms on disease susceptibility and clinical features. Ninety-nine Behçet’s disease (BD) patients and 114 controls were genotyped to analyze three single nucleotide polymorphisms (SNPs) including A126G, G155A, and A161G of the IL-17F gene using automated sequencing. We compared the frequencies of IL-17F alleles, genotypes, and haplotypes in patients with BD and controls using the chi-square or Fisher’s exact test. Significant differences in the frequencies of allele and genotype in A126G SNP of IL-17 gene were found between BD patients and controls (P < 0.001 and P < 0.001, respectively). None of three IL-17F SNPs were associated with diverse clinical features in BD. The frequency of haplotype AA did not differ between patients with BD and controls (P = 0.985). The haplotypes, AG, and GG, have positive and inverse association with BD susceptibility (P < 0.001 and P < 0.001, respectively). These findings suggest that IL-17 gene SNPs may influence the susceptibility of BD.     

白细胞介素-2基因多态性与慢性乙型肝炎的相关性

目的 探讨白细胞介素-2(IL-2)基因多态性与慢性乙型肝炎的相关性,以及对HBVDNA水平的影响.方法 应用聚合酶链反应-限制性片段长度多态性分析和DNA测序的方法检测155例慢性乙型肝炎患者和170名健康对照者的IL-2基因-385T/G、+114T/G单核苷酸多态性位点基因型,血清HBV DNA测定采用荧光定量PCR技术.结果 IL-2基因+114T/G多态性在慢性乙型肝炎组和正常人群中的频率分布差异无统计学意义.IL-2基因-385T/G多态性在两组人群中的频率分布差异有统计学意义,X2=7.377,P<0.05.等位基因频率的相对风险分析发现,G等位基因携带者患慢性乙型肝炎的风险是T等位基因的1.490倍(OR=1.490,95%CI:1.085-2.046);进一步比较慢性乙型肝炎患者IL一2基因多态性与HBV DNA复制的关系,发现高水平HBVDNA(≥1×10<'3>拷贝/ml)组-385G等位基因携带者分布频率明显高于低水平HBV DNA组(<1×10<'3>拷贝/ml),X2=6.051,P=0.014,差异有统计学意义.结论 IL-2基因-385T/G多态性可能与HBV具有相关性,其中G等位基因可能是慢性乙型肝炎的遗传易感基因,携带G等位基因的个体可能更利于HBV DNA的复制.     

Polymorphisms of the TAP2 transporter gene in systemic lupus erythematosus.

OBJECTIVES--To determine whether the TAP2 transporter gene, which lies between HLA-DP and HLA-DQ, is involved in determining susceptibility to systemic lupus erythematosus (SLE). METHODS--TAP2 types were determined by ARMS-PCR in 89 white patients with SLE and 156 control subjects. RESULTS--No particular TAP2 dimorphism or allele was associated with SLE or with any clinical/immunological subgroup of SLE. Furthermore, there was no evidence for significant linkage disequilibrium between TAP2 and HLA-DQ/DR in SLE. CONCLUSIONS--These data suggest that TAP2 is not a disease susceptibility gene for SLE and that the disease-predisposing haplotypes do not extend as far as TAP2. This indicates that any HLA-DP association with SLE must be independent of other class II (DQ/DR) associations.     

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。     

HLA DQA1-DQB1-TAP2 haplotypes in IDDM families: no evidence for an additional contribution to disease risk by the TAP2 locus

Summary The TAP2 gene, located in the HLA class II region, encodes a subunit of a transporter involved in the endogenous antigen-processing pathway, and has been suggested to contribute to the genetic risk for insulin-dependent diabetes (IDDM). In order to determine whether the TAP2 locus modulates the risk conferred by HLA DQ loci, HLA DQA1-DQB1-TAP2 haplotypes were analysed in 48 IDDM probands, their first degree relatives, and in 62 normal control subjects. A decreased frequency of the TAP2B allele was confirmed in this IDDM cohort (12 vs 28% in control subjects, p _c <0.05). Analysis of 73 informative meiotic events in IDDM and control families demonstrated a recombination fraction between HLA DQB1 and TAP2 loci of 0.041 (Log of the odds score=16.5; p<10^–8) indicating strong linkage between these loci. Family haplotype analysis demonstrated linkage disequilibrium between TAP2 and HLA DQA1-DQB1, and showed that the reduced frequency of TAP2B was associated with its absence on the IDDM susceptible DQA1*0301-DQB1*0302 haplotype, its low frequency on DQA1*0501-DQB1*0201, and the association of TAP2B with DQA1*0101-DQB1*0501 haplotypes which were less frequent in IDDM patients. Comparison of transmitted with non-transmitted haplotypes in IDDM families showed a slight but not significant decrease in TAP2B allele frequency on transmitted (3 of 37) vs non-transmitted (2 of 9) HLA DQA1*0501-DQB1*0201 haplotypes. No other differences were observed. Twenty-four unrelated DQA1*0501-DQB1*0201 haplotypes from non-diabetic families had a TAP2B allele frequency (4%) similar to that in IDDM haplotypes. These findings suggest that the decreased TAP2B allele frequency in Italian IDDM patients is due to HLA DQ haplotype differences between IDDM patients and control subjects, and do not support a contribution to IDDM risk by the TAP2 locus.Abbreviations ARMS Amplificatory refractory mutation system - IDDM insulin-dependent diabetes mellitus - MHC major histocompatibility complex - PCR polymerase chain reaction - TAP transporter associated with antigen processing     

Association of TAP1 and TAP2 polymorphisms with the outcome of persistent HBV infection in a northeast Han Chinese population

Abstract

Objective. Transporter associated with antigen processing (TAP) plays a central role in a cellular immune response against HBV. Polymorphisms exist at the coding region of TAP and alter its structure and function. The aim of this study was to evaluate the potential relationship between polymorphisms of TAP and different outcomes of persistent HBV infection in a Han population in northeastern China. Material and methods. 189 HBV spontaneously recovered (SR) subjects, 571 HBV-infected patients including 180 chronic hepatitis B (CHB), 196 liver cirrhosis (LC) and 195 hepatocellular carcinoma (HCC) individuals were included in this study. TAP1-333 Ile/Val and -637 Asp/Gly, TAP2-651 Arg/Cys and -687 Stop/Gln were genotyped in all the samples by using a PCR-RFLP method. Results. The frequency of TAP1-637-Gly (allele G) was significantly higher in persistently HBV-infected individuals (CHB and LC) than that of SR subjects (OR = 1.58, 95% CI 1.12–2.45, p = 0.024; OR = 1.78, 95% CI 1.27–2.68, p = 0.002) by a logistic regression analysis. In addition, the statistically significant difference in the distribution of TAP2-651-Cys (allele T) was observed between HCC cases and SR controls (OR = 2.30, 95% CI 1.51–3.72, p < 0.001), and TAP2-687-Gln (allele C) in CHB patients was more common than that in SR subjects (OR = 1.41, 95% CI 1.13–1.97, p = 0.021). The data also revealed that haplotype 687 Gln-651 Cys-637 Gly-333 Ile was strongly associated with persistent HBV infection (CHB, LC and HCC) (p < 0.001, < 0.05 and < 0.001, respectively). Conclusion. These results suggested that TAP variants were likely to play a substantial role in different outcomes of persistent HBV infection in the studied population.     

Association of polymorphisms of interleukin-18 gene promoter region with chronic hepatitis B in Chinese Han population

AIM: To investigate the polymorphisms of interleukin-18 (IL-18) gene promoters, and to disclose whether such polymorphisms are associated with susceptibility to chronic hepatitis B in Chinese Han population. METHODS: Using polymerase chain reaction with sequence specific primers (PCR-SSP) method, the single nucleotide polymorphisms (SNPs) of the promoter region of IL-18 gene at position -607 and -137 were detected in 231 patients with chronic hepatitis B and 300 normal controls. RESULTS: Allele C at position -607 in the promoter of IL-18 gene was detected in 48.7% of normal controls and 51.9% of patients, while allele A at position -607 was detected in 51.3% of normal controls and 48.1% of patients. The frequencies of -607CC, -607 CA and -607AA genotypes in normal controls were 22.0%, 53.3% and 24.7% respectively and in chronic hepatitis B patients were 26.8%, 50.2% and 23.0% respectively. Allele G at position -137 in the promoter of IL-18 gene was detected in 82.3% of normal controls and 88.5% of chronic hepatitis B patients, while allele C at position -137 was detected in 17.7% of normal controls and 11.5% of patients. The frequencies of -137GG, GC and CC genotype were 67.3%, 30.0% and 2.7% in normal controls respectively, while in chronic hepatitis B patients were 78.8%, 19.5% and 1.7% respectively. The frequency of-137GG genotype in chronic hepatitis B groups was significantly higher than that in normal controls (x2=8.55, P=0.003 <0.05), whereas the frequencies of -607C/-137C and -607A/-137C haplotypes in chronic hepatitis B groups were significantly lower than that in normal controls. The association between genotypes of IL-18 promoter region polymorphisms and HBV copies showed that the frequency of -607AA genotype in high HBV-DNA copies groups was lower than that in low HBV-DNA copies groups (x2=6.03, P=0.014 <0.05). CONCLUSION: The polymorphisms of the promoter region of IL-18 gene at position -607 and -137 are closely associated with susceptibility to chronic hepatitis B. The people with allele C at position -137 in the promoter of IL-18 gene may be protected against HBV infection; moreover AA genotype at position -607 may be closely linked to inhibit HBV-DNA replication. These findings give some new clues to the study of pathogenesis of chronic hepatitis B.     

Influence of tissue factor polymorphisms (603A>G and 5466A>G) on plasma tissue factor levels and their impact on deep vein thrombosis risk in young Indian population

Deep vein thrombosis (DVT) is multifactorial disorder and well known to cause substantial morbidity and mortality. There is sparse data in the Asian population, particularly India regarding association of tissue factor (TF) gene single nucleotide polymorphisms (SNPs) with plasma TF levels in DVT. So, we analyzed the distribution of SNPs (603A>G and 5466A>G) in India, to evaluate their effect on TF levels in DVT patients. Plasma level and SNPs (603A>G and 5466A>G) of TF gene were screened in subjects (100 DVT patients and 100 controls). Patients had significantly higher TF levels than controls (patients: 84.95?±?17.16 pg/ml, controls: 70.55?±?15.87 pg/ml, p?G polymorphism was significantly higher in patients than controls (patients: 40.5% controls: 27.5%, p?=?0.004). Subjects with AG and GG genotype had significantly higher TF levels than AA genotype (p?=?0.001). After multiple logistic regression analysis, risk of DVT was increased 1.398 fold (95% CI 0.738–2.651) and 4.41 fold (95% CI 1.404–13.884) with AG and GG genotype respectively. Allelic and genotypic frequencies of 5466A>G polymorphism was neither associated with TF levels nor with DVT. We found high TF level in patients with TF 603A>G polymorphism, which is an important predisposing factor in increasing risk of DVT in young Indians. Furthermore, GG genotype of 603A>G polymorphism augments the risk of thrombosis by 4.4 fold, thus highlighting the significance of this polymorphism in the development of DVT. So, we suggest that inclusion of 603A>G polymorphism in prothrombotic work-up may be helpful in making the treatment strategy in DVT patients.     

Gonadectomy alters myosin heavy chain composition in isolated cardiac myocytes

A total of 95 patients with Graves’ disease (GD) and 105 normal healthy controls were enrolled in this study to determine how a single site polymorphism of the transporter associated with antigen processing 1 (TAP1) gene contributes to the pathogenesis of GD. The polymorphism was detected using polymerase chain reaction (PCR)-based restriction analysis. Associations between GD and the two-site polymorphisms of the TAP1 gene at codons 333 and 637 were evaluated. No significant differences were revealed comparing GD patients and normal individuals for the distributions of genotypes and allelic variants at codon 333 (p=0.253 and p=0.891, respectively). By contrast, the distributions for the AA homozygote at codon 637 were reduced and those for the GA heterozygote were increased comparing the two groups (p<0.0001). The allelic analysis also demonstrated lower A and higher G allele frequencies (p=0.0008; OR=2.745, 95% CI=1.482-5.085) comparing the GD patients with the normal healthy controls. This shows that the single-site polymorphism of the TAP1 gene at codon 637 may be an indicator for predicting development of GD.