干扰素γ基因内含子1+874位点多态性与乙型肝炎病毒感染关系的研究

目的 研究干扰素γ（IFN-γ）基因内含子1＋874位点多态性与乙型肝炎病毒（HBV）感染、转归的关系,探讨慢性HBV感染的遗传易感因素.方法 采用序列特异性引物-聚合酶链反应（PCR-SSP）技术检测231例慢性HBV携带患者、165例自限性HBV感染者和135名正常对照者IFN-γ基因内含子1＋874位点T/A单核苷酸多态性.结果 慢性HBV感染组IFN-γ基因＋874位点AA基因型频率（TT、TA、AA频率分别为9.1%、12.1%、78.8%）高于正常对照组（TT、TA、AA频率分别为12.6%、23.0%、64.4%）（x2=9.60,P=0.008）;而自限性HBV感染组（TT、TA、AA频率分别为13.9%、23.7%、62.4%）和对照组之间差异无显著性（x2=0.16,P=0.92）.结论 IFN-γ基因内含子1＋874位点多态性与慢性HBV感染有关,该位点多态性可能在决定个体HBV感染遗传易感性方面有一定意义.     

TNF-α及IL-6基因多态性与胃腺癌易感性的关系

目的:探讨肿瘤坏死因子 α（TNF α）和白细胞介素 6（IL 6）基因单核苷酸多态性（SNP）与胃腺癌及幽门螺杆菌（HP）感染胃腺癌发生发展的相关性。方法:采用基因芯片技术检测65例胃腺癌患者和71例健康对照人群中TNF α 238G/A、 308G/A和IL 6 597G/A、-174G/C、-572G/C位点多态性。同时应用酶联免疫吸附试验（ELISA）测定其血清中HP IgG/IgM/IgA型抗体浓度。结果：感染HP胃腺癌患者的阳性率明显高于感染HP的对照组(P=0.007, 相对危险度［OR］=2.53，95%可信区间［95%CI］=1.28-5.24)。胃腺癌组TNF α 238GA基因型和A等位基因频率明显高于对照组(P=0.024， OR=2.44， 95%CI=1.11-5.37; P=0.039， OR=2.13， 95%CI=1.03-4.41)，在HP阳性胃腺癌组明显高于HP阴性胃腺癌(P<0.05，OR=4.53,　95%CI=1.16-17.68; P<0.05，OR=3.52,　95%CI=0.98-12.64)。胃腺癌组IL 6 572CC基因型频率明显低于对照组(P=0.014，OR=0.17，95%CI=0.04-0.81)。未见TNF α和IL 6其他位点的SNP与胃腺癌组或HP阳性胃腺癌组有任何相关性。结论：TNF 238GA基因型及其等位基因A与胃腺癌或感染HP的胃腺癌易感性相关，而IL 6 572CC基因型则能降低胃腺癌易感性。     

CYP1A1基因多态性与子宫内膜腺癌发生的关系研究

目的研究细胞色素P4501A1(CYP1A1)基因MspI位点和Ile-Val位点多态性与子宫内膜腺癌发生的关系。方法以病例-对照研究,采用聚合酶链反应-限制性片段长度多态性分析(PCR-RFLP)方法和等位基因特异性PCR(AS-PCR)技术检测84例子宫内膜腺癌患者和66例对照者CYP1A1基因MspI位点和Ile-Val位点的多态性。结果Ile-Val三种多态基因型在对照组和子宫内膜腺癌组中的分布在显著性差异(P<0.05),其中Ile/Val和Val/Val基因型在子宫内膜腺癌组中的分布频率明显高于对照组。与Ile/Ile基因型相比,Ile/Val基因型个体发生子宫内膜腺癌的相对危险度(OR)是2.682,两者差异有统计学意义(P<0.05);而MspI位点的多态性在对照组和子宫内膜腺癌组中的分布差异无统计学意义(P>0.05)。结论CYP1A1基因第7外显子的Ile/Val基因型与子宫内膜腺癌的发生有关,可以作为子宫内膜腺癌易感人群筛查的重要指标,MspI位点多态性与子宫内膜腺癌的发生无相关性。     

LMP2基因多态性及夫妻共享率与重度子痫前期的相关性研究

目的 测定重度子痫前期（severe pre-eclampsia，S-PE）患者和正常孕妇多功能蛋白酶（large muhifunctional protease，LMP2）基因多态性及夫妻共享率，探讨该基因与S-PE发病的相关性。方法 选择102例S-PE患者及其配偶为研究对象，随机选择200例正常孕妇及其配偶作为对照。所选孕妇均为单胎初孕，孕35～40周。各取2ml外周静脉血抽提DNA，应用PCR—RFLP方法进行LMP2基因分型。结果 LMP2R／H在S-PE患者中的分布频率显著高于正常孕妇组（53．9％和35．5％，P〈0．01），LMP2R／R在S-PE患者中的分布频率显著低于正常孕妇组（41．2％和58．5％，P〈0．01）。LMP2R／H在S-PE组的夫妻共享率与正常孕妇组的相比显著增高（24．5％和10．5％，P〈0．01）。结论 LMP2R／H很可能为S-PE发病的易感基因；而LMP2R／R可能是S-PE的保护基因。     

TNF-a与2型糖尿病胰岛素抵抗的关系

目的:探讨血清肿瘤坏死因子-α(TNF-α)水平以及TNF-α基因多态性与2型糖尿病胰岛素抵抗的关系。方法:选取2型糖尿病肥胖患者50例,非肥胖患者50例,健康对照50例,应用酶联免疫法检测血清中TNF-α水平,并应用PCR-RFLP方法检测TNF-α-308启动子区基因多态性,所有数据以SPSS 10.0软件进行分析。结果:糖尿病肥胖组血清TNF-α水平较非肥胖组及对照组明显增高,在糖尿病组中TNF-α-308A等位基因携带者体质指数(BMI)及胰岛素抵抗均高于TNF-α-308G等位基因携带者。结论:TNF-α与BMI和胰岛素抵抗明显相关。携带TNF-α-308A等位基因者更易于发生胰岛素抵抗。     

XRCC1单核苷酸多态及单体型分布与乳腺癌的相关研究

目的：探讨X线交叉互补基因1（XRCC1）外显子C26304T、G27466A和G28152A三处最常见的单核苷酸多态性（single nucleotide polymorphism，SNP）与乳腺癌的关系。方法：以自然人群为基础的病例对照研究方法，对84例乳腺癌患者组和以1：3成组频数匹配原则获得的252例对照组进行研究，XRCC1 C26304T、G27466A和G28152A SNPs基因分型采用聚合酶链反应-限制性内切酶片段长度多态性（polymerase chain reaction—restriction fragment length polymorphism，PCR—RFLP）分析方法。单体型分布采用EH linkage software 1．2分析软件进行预测和比较。结果：乳腺癌患者组和对照组吸烟状况分布差异有显著性，病例组曾经或现在吸烟个体比例7．1％明显高于对照组2．0％（P〈0．05），性别、年龄、饮酒状况及一二级亲属家族恶性肿瘤史等基本特征因素分布差异均无显著性（P〉0．05）。C26304T、G27466A和G28152A SNPs多态基因型和多态等位基因分布在两组间分布差异均无显著性（P〉0．05）。经上述因素校正后，XRCC1 SNPs与乳腺癌发病没有显著相关关系（P〉0．05）。应用EH linkage software 1．2单体型分析软件显示，XRCC1 SNPs在各组内均存在连锁不平衡现象，CGG、CGA、CAG和TGG是最常见的4类单体型。单体型组间分布同样不存在显著性差异（P〉0．05）。结论：XRCC1 C26304T、G27466A和G28152A SNPs与乳腺癌的风险没有相关关系，各SNPs存在连锁不平衡现象，CGG、CGA、CAG和TGG是最常见的4类单体型。     

Association between microRNA polymorphisms and chronic pancreatitis

BackgroudMicroRNAs play important roles in the development and progression of many human diseases. mir-146a could significantly suppress the induction of proinflammatory cytokines IL-1β, IL-6, TNF-α, NF-κB and chemokine MCP-1, which might play important roles in chronic pancreatitis. This study was conducted to evaluate the association between mir-146a rs2910164, a functional polymorphism in the pre-mir-146a, and chronic pancreatitis risk.MethodsThe rs2910164 genotypes were determined in 165 patients with chronic pancreatitis and 200 healthy controls who were frequency matched for age and gender. One single nucleotide polymorphism (rs2910164) was genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RLFP).ResultsThe frequency of individuals who carried [G] allele was significantly higher in cases (62.7%) than in controls (53.7%, p = 0.015), which resulted in a statistically significant pathogenic effect associated with this variant allele (OR: 1.448, CI: 1.076–1.950; p = 0.015). The GC and GG genotypes showed strong and significant increased risk for complication of chronic pancreatitis (OR = 3.668, 95%CI = 1.233–10.916, p = 0.019; OR = 5.667, 95%CI = 1.852–17.336, p = 0.002). The individuals carrying G allele confer a lower expression level of mature mir-146a.ConclusionThese findings suggest that the mir-146a rs2910164 may contribute to genetic susceptibility to chronic pancreatitis, and that mir-146a might be involved in chronic pancreatitis development.     

Fcγ receptor 3B polymorphism is associated with hypersensitivity reactions to adalimumab in Japanese patients with rheumatoid arthritis

Objectives: To examine the association between Fcγ receptor (FcγR) polymorphisms and the development of hypersensitivity reactions to adalimumab in patients with rheumatoid arthritis.

Methods: Sixty-five patients receiving adalimumab were enrolled in the study. Genetic polymorphisms for FcγR3B were genotyped in FCGR3B NA1/2 alleles by real allelic discrimination assay. Clinical information and the occurrence of a hypersensitivity reaction to adalimumab were collected from the patients’ charts.

Results: A hypersensitivity reaction was observed in 12% of the patients. Clinical information obtained from patients with a reaction and those without were the same. The FCGR3B NA1/NA1, NA1/NA2, and NA2/NA2 alleles were found in 75%, 13%, and 13% of the patients with hypersensitivity reaction, respectively, and in 28%, 42%, and 30% of those without a hypersensitivity reaction, respectively (p?=?0.04). Multivariate logistic regression analysis identified only the NA1/NA1 as an independent relevant factor for a hypersensitivity reaction to adalimumab (OR 7.7, p?=?0.01).

Conclusions: The FCGR3B NA1/NA1 genotype is associated with hypersensitivity reactions to adalimumab.     

FAS-670A/G多态性与宫颈癌易感性的Meta分析

目的探讨FAS-670A/G多态性与宫颈癌易感性之间的关系。方法全面检索相关文献,收集2012年1月前有关FAS-670A/G多态性与宫颈癌易感性的病例对照研究,使用Stata 10.0进行Meta分析。结果最终纳入病例对照研究10项,累计病例2174例,对照2514例。在显性模型、隐性模型、加性模型中,Meta分析的OR值及95%CI分别为1.08（0.83-1.41）、0.99（0.76-1.30）、1.03（0.91-1.17）,且按种族所进行的分层分析中各OR值均未达到显著性水平。结论 FAS-670A/G多态性与宫颈癌易感性之间无显著关联。