唐山地区汉族人群脑梗死患者IL-6基因-572C/G多态性研究

目的:探讨唐山地区汉族人群脑梗死患者IL-6基因-572C/G多态性及其分布特点。方法:应用聚合酶链反应(PCR)和限制性片段长度多态性(RFLP)方法测定唐山地区汉族人群中157例脑梗死患者的IL-6基因-572C/G的基因多态性。结果:脑梗死患者和健康人群的C等位基因频率均明显高于G等位基因频率(P0.05)。经Hardy-Weinberg吻合度检验,脑梗死人群和健康人群的-572C/G位点基因型个体数的观察值和期望值差异均无显著性(P0.05)。本组脑梗死患者人群和健康人群中不同性别之间IL-6-572C/G的基因型及等位基因频率分布的差异均无统计学意义(P0.05)。结论:唐山地区汉族人群脑梗死患者中可能存在IL-6基因-572C/G多态性,C等位基因可能为常见基因,G等位基因可能为少见基因。     

IL-6/IL-6受体与类风湿关节炎关联性研究新进展

IL-6是一种多效性前炎症细胞因子,有多种生物活性,包括介导炎症反应,免疫反应等。IL-6在许多炎症性疾病中高表达,如RA,SLE,Crohn’s病等。IL-6的产生受多种因素的调节如NF-κB,Lin28,let-7 microRNA,IL6阳性反馈环,JunB等。IL-6受体(IL-6R)包括特异性IL-6Rα及IL-6Rβ即IL-6家族成员共有的信号转导蛋白gp130。IL-6可通过两种途径向细胞内传导信号:传统途径及反式信号途径,LMO4可参与反式信号途径的调节。IL-6/IL-6R在T、B细胞的发生中起重要作用。IL-6可抑制Th1、Treg的分化,促进Th2的分化;而且IL-6是CD4+T细胞分化为Th17细胞所必需;在B细胞中IL-6可诱导RAG基因的表达,促进抗体的产生。近年来越来越多的证据表明IL-6/IL-6R与RA存在密切关联性。RA患者血清及滑液中IL-6及sIL-6R的浓度升高,并且IL-6水平与疾病活性及临床表现密切相关,这可以解释RA患者的许多症状。因此可将IL-6信号转导途径相关的分子作为RA的治疗靶点,目前也研制出几种药物,其中之一为抗sIL-6R的人源化抗体Tocilizumab。临床试验中,该药可减轻RA患者的症状,降低疾病活性,可是也带来一定的副作用,这就限制了该药在临床中的应用。正在研制的另一种抗IL-6R的抗体可能为干预RA带来新的希望。     

广西壮族与汉族IL-6基因启动子-634C/G多态性的研究

目的研究白细胞介素-6(IL-6)基因启动子-634C/G多态性在中国广西壮、汉两民族中的分布.方法应用聚合酶链反应-限制性片段长度多态性技术检测185名壮族人和198名汉族人的白细胞介素-6基因启动子-634C/G多态性,比较两组白细胞介素-6基因型和等位基因的分布频率.结果在壮族人中CC、CG和GG基因型分别为69.7%、28.7%和1.6%;在汉族人中CC、CG和GG基因型分别为68.2%、29.3%和2.5%.两组白细胞介素-6基因型的分布频率差异无显著性(P＞(0.05).结论壮族与汉族白细胞介素-6基因-634C/G多态性分布频率差异无显著性.     

白细胞介素6基因-572C/G多态性与心肌梗塞易感性的关联研究

目的观察白细胞介素6（interleukin 6，IL6）基因-572C／G多态性在中国人群中的分布频率、与心肌梗塞（myocardial infarction，MI）易感性的关系、对MI患者冠脉病变程度的影响以及初步对该位点基因变异进行功能性分析。方法应用聚合酶链反应．限制性片段长度多态性方法对232例MI患者和260名正常对照者IL6基因-572C／G多态性进行了分析，观察了该基因多态性对冠脉病变程度及外周血单核细胞（peripheral blood mononuclear cells，PBMC）产生IL6能力的影响。结果中国汉族人群存在IL6基因-572C／G多态性；两组人群基因型、等位基因频率差异存在统计学意义，MI组CG＋GG基因型频率、G等位基因频率均显著高于对照组（P〈0．01）；基因型频率的相对风险分析发现，G等位基因携带者息MI的风险是CC基因型的1．68倍（95％CI：1．17—2．41，P〈0．01）；-572C／G多态性在单支、双支、三支冠脉病变组间的分布差异无统计学意义（P〉0．05）；G等位基因携带者氧化低密度脂蛋白刺激24h PBMC产生IL6的能力明显高于CC基因型（P〈0．05）。结论IL6基因-572G等位基因可能是中国汉族人MI的易感因子，这可能与携带该等位基因的人群存在IL6水平的高表达有关。     

中国汉族人群IL-1RA基因多态性及其与宫颈癌的相关性研究

目的 研究位于白细胞介素1受体拮抗剂基因（interleukin-1 receptor antagonist, IL-1RA）第二个内含子中可变串连重复序列（variable number of tandem repeats, VNTR）多态性在中国3个汉族人群中的分布情况,并探讨其与宫颈癌的发生关系。方法 采用PCR方法分别对3个汉族人群206例个体以及42例宫颈癌患者和45例对照进行多态性检测,扩增产物进行2％的琼脂糖电泳。结果 三个汉族群体的基因型以A1/A1和A1/A2最为常见。等位基因以A1频率最高,A2次之,群体间的差异是不显著的（P＞0.05）。与美、英高加索人群相比,A1 的频率明显偏高,A2明显偏低,而与非洲黑人相近。在宫颈癌患者和正常对照人群中,该多态位点的等位基因和基因型频率均无统计学意义（P＞0.05）。结论 IL-1RA第二个内含子中 VNTR多态性在不同种族间的分布存在着明显的差异,但与中国东北地区宫颈癌的发生可能无直接相关性。     

白细胞介素-6基因-572C/G基因型与外周血血小板数量的相关性研究

目的 :观察IL 6基因 -5 72C/G多态性对健康人群外周血血小板数量的影响。方法 :采用聚合酶链反应 限制性片段长度多态性分析方法测定我院门诊体检的 2 0 3例健康人群的IL 6基因 -5 72C/G多态性 ,分析其与外周血血小板数量的关系。结果 :-5 72C/G多态性与人群中外周血血小板数量相关 ,G等位基因携带者血小板数量明显高于CC基因型者 ( 188.2 3± 5 2 .5 6× 10 9·L- 1 vs 181.3 0± 5 0 .10× 10 9·L- 1 ,P <0 .0 5 ) ,而两组间年龄、性别、体重指数、血压、血糖、胆固醇、甘油三脂、白细胞数量及分类等一般临床和生化特征均无差别 (P均 >0 .0 5 )。结论 :IL 6基因 -5 72C/G多态性可以影响健康人群外周血血小板数量水平 ,G等位基因携带者血小板水平较高 ,这在血栓性疾病的一级预防中具有一定意义     

IL-4R、IL-13、ADAM33基因多态性与中国皖南地区汉族人群支气管哮喘的相关性研究

目的:探讨IL-4受体基因Arg551Gln(rs1801275)、IL-13基因Arg130Gln(rs20541)、ADAM33基因T1(rs2280091)位点基因多态性与中国皖南地区汉族人群支气管哮喘的相关性。方法:采用病例-对照的方法,用聚合酶链反应及直接基因测序法比较116例支气管哮喘组与70例正常人对照组之间基因型、等位基因频率的差异。结果:哮喘组和对照组IL-4受体基因Arg551Gln位点和IL-13基因Arg130Gln位点的基因型和等位基因型频率的差异有统计学意义,ADAM33基因T1位点基因型哮喘组和对照组差异有统计学意义,等位基因型频率在哮喘组和对照组差异无统计学意义。结论:提示IL-4R Arg551Gln(rs1801275)位和IL-13基因Arg130Gln(rs20541)位的多态性可能与中国皖南地区汉族哮喘有相关性;ADAM33基因(rs2280091)T1位点位的多态性可能与中国皖南地区汉族哮喘无相关性。     

慢性乙型肝炎病毒感染与HLA-DRB1基因的相关性研究

目的： 研究HLA-DRB1等位基因与HBV感染慢性化的相关性。 方法： 用PCR-SSP 方法对陕西地区汉族乙肝患者108例与正常对照108人以及慢性乙型肝炎表面抗原携带者32人，进行HLA-DRB1等位基因分型比较，并进行HLA-DRB1等位基因分型与HBV不同复制状态相关性分析。 结果： 陕西地区汉族人HLA-DRB1等位基因以DRB1*04（16.2%），DRB1*09（12.5%），DRB1*12（11.6%）, DRB1*15（13.4%）最为常见；病例组HLA－DRB1*03 的等位基因频率(10.6%)明显高于健康对照组(3.7%)，(OR=3.10; P<0.05)；HLA-DRB1*07等位基因频率病例组(17.6%)明显高于健康对照组(9.3%)(OR=2.09; P<0.05)；DRB1*07 基因位点在HBV高复制状态多见（OR=2.22; P<0.05）; HLA-DRB1*15对照组等位基因频率13.4%, 明显高于病例组6.9% (OR=0.48; P<0.05)。 结论： HLA－DRB1*03、HLA-DRB1*07与陕西地区汉族人HBV感染后的慢性化相关联，HLA-DRB1*15为陕西地区汉族人乙肝感染的抗性基因。本研究提示HLA-Ⅱ类基因是决定HBV感染后临床转归的重要因素。     

吉林汉族人群乙型肝炎肝硬化患病与HLA-DRB1等位基因的关联性

目的：探讨吉林地区汉族人群乙型肝炎肝硬化患病与白细胞抗原（HLA）DRB1区等位基因多态性的关联性。方法：采用PCR-SSP方法对吉林地区汉族61例慢性乙型肝炎,44例乙型肝炎肝硬化患者,32名HBV感染自然恢复者及50名健康献血员作对照进行了HLA-DRB1等位基因分型比较。结果：慢性乙型肝炎组HLA-DRB1＊1201-3等位基因表达频率为17.21%,明显高于正常对照组8.00%（P=0.0427,RR=2.391）；慢性乙型肝炎组与乙型肝炎肝硬化组HLA-DRB1＊0701等位基因频率分别为11.48%,12.50%,明显高于正常对照组2.00%（P=0.0066,RR=6.35；P=0.0046,RR=7.00）及HBV感染自然恢复组1.56%（P=0.0183,RR=8.17；P=0.0136,RR=9.00）；而所检测HLA-DRB1座位的其它等位基因表达频率在四组间无显著性差异（P〉0.05）。结论：吉林地区汉族人群慢性乙型肝炎患病与HLA-DRB1＊1201-3、HLA-DRB1＊0701等位基因型相关联；而乙型肝炎肝硬化患病仅与HLA-DRB1＊0701等位基因型相关联。     

MxA基因启动子区-88G/T、-123C/A单核苷酸多态性与HCV易感性和IFN-α疗效评价研究

目的:研究黏病毒抗性蛋白(MxA)启动子区-88(G/T)、-123 (C/A)位点单核苷酸多态性(SNP)与汉族人群丙型肝炎病毒(HCV)的易感关联性,同时探讨各基因型与PEG-IFNα-2α抗病毒疗效的相关性.方法:应用聚合酶链反应(PCR)及限制性片段长度多态性(RFLP)方法检测46例慢性丙型肝炎患者(CHC组)和50名健康者(HC组)的MxA基因启动子-88和-123位点基因型,以生化、病毒学应答率(RVR、EVR、ETVR、SVR)为疗效评价指标.结果:-88/-123位点各基因型及等位基因在CHC组与CH组中的分布频率差异无统计学意义(P＞0.05),MxA-88位点等位基因T和-123位点等位基因A可能与HCV易感性无关(OR95％CI分别为0.60～1.96;0.35 ～ 1.14).ALT水平随HCV-RNA载量的增加而升高,呈正相关(r=0.931).HCV病毒载量和ALT水平分别在-88或-123位点不同基因型间比较,差异无显著性(P＞0.05).-88G/T、-123C/A和MxA-88/-123间的IFN-α治疗应答反应率差异无统计学意义(P＞0.05).结论:MxA-88G/T和-123C/A位点SNP与HCV易感性无明显关联性,但MxA-88T/-123A变异基因可能间接增加HCV感染的风险,且MxA-88T变异基因可能与IFN-α抗病毒疗效和HCV感染后结局有关.     

HLA-DRB1*07与慢性乙肝患者Th1/Th2因子表达水平的相关性

目的 :探讨广东地区汉族慢性乙型肝炎患者HLA DRB1 0 7与Th1 Th2因子表达水平的相关性。方法 :收集 12 0例广东地区汉族慢性乙肝患者新鲜抗凝血各 8ml,通过序列特异性引物套式PCR(PCR SSP)方法进行HLA DRB1 0 7检测 ,并同时用双抗体夹心法检测患者治疗前后外周血CD4 +T细胞分泌IFN γ、IL 2、IL 10和IL 4的水平。结果 :12 0例慢性乙肝患者HLA DRB1 0 7携带者 31例 ,携带率为 2 5 8% ,明显高于广东地区汉族人群的平均携带率 7 84 % ;HLA DRB1 0 7阳性患者IFN γ平均表达水平为 (1132 0 4± 75 36 )pg ml,IL 2平均表达水平为 (1184 0 6± 81 4 2 )pg ml,IL 4平均表达水平为 (876 79± 4 7 5 3)pg ml,IL 10平均表达水平为 (817 4 8± 2 4 4 0 )pg ml ;HLA DRB1 0 7阴性患者IFN γ平均表达水平为 (12 32 10± 198 13)pg ml,IL 2平均表达水平为 (12 0 8 17± 116 12 )pg ml,IL 4平均表达水平为 (6 81 99± 6 1 5 9)pg ml,IL 10平均表达水平为 (6 38 84± 76 17)pg ml。HLA DRB1 0 7阳性患者IL 4、IL 10表达水平高于阴性患者 (P <0 0 5 ) ,而IFN γ、IL 2表达水平与阴性患者差异无统计学意义 (P >0 0 5 )。结论 :HLA DRB1 0 7(+)慢性乙肝患者Th2因子表达水平高于HLA DRB1 0 7(- )慢性乙肝患者。     

南方人群HBV感染与HLA-DQB1基因的相关性研究

目的：了解HLA-DQB1与广州地区HBV感染的关系。方法：PCR-SSO基因分型技术，对南方人群中63个不相关的正常个体和63个不相关HBV感染患者（HbsAg、HBeAg、HbcAb检测阳性）HLA-DQB1位点进行了基因分型调查。结果：两者的HLA-DQB1的各等位基因表现型频率无显著差异。结论：南方人群HBV感染与HLA-DQB1无显著相关性。     

慢性乙型肝炎患者血清HBVDNA含量和IL-12对其PBMC产生Th1/Th2类细胞因子影响的相关性研究

目的：研究慢性乙型肝炎患者血清HBVDNA含量对IL－12诱导其PBMC产生Th1/Th2类细胞因子协同效应的影响。方法：分离50例慢性乙型肝炎患者外周血单个核细胞，分别与PHA（100μg/ml）、HBcAg（1μg/ml）、HBeAg（1μg/ml）单独或联合IL－12（10ng/ml）体外培养48h，ELISA法检测培养上清液细胞因子IL－2、IFN－γ、IL－10。荧光定量PCR检测患者血清DNA含量，并分成HBVBDNA小于10^3拷贝／ml、1063-10^5拷贝／ml、1065-10^7拷贝／ml、大于10^7拷贝/ml4组。结果：以HBVDAN小于10^3拷贝／ml组做对照组，比较发现无论抗原（PHA、HBcAg、HBeAg）单独诱导还是联合IL－12共同诱导，随着血清HBVDNA含量的增高，PBMC产生IL－2和IFN-γ水平逐渐降低，产生IL－5和IL－10水平逐渐升高，并且IL－12对PBMC产生IFN－γ的增殖效应逐渐减弱，特别是血清HBVDNA大于10^7拷贝／ml患者几乎无明显增殖效应。结论：高水平血清HBVDNA含量对IL－12诱导慢性乙型肝炎PBMC产生IFN－γ协同效应有抑制作用。     

In vitro IL-6 production by EBV-immortalized B lymphocytes from young and elderly people genotyped for -174 C/G polymorphism in IL-6 gene: a model to study the genetic basis of inflamm-aging

In the present investigation we analysed Interleukin 6 (IL-6) in vitro production by Epstein-Barr virus (EBV)-immortalized B lymphocytes established from 43 subjects, 15 young people and 28 elderly people, including 18 centenarians, after 3, 6, 9, 24, 48 and 72 h of culture. The subjects were genotypized for the C to G transition at nucleotide -174 of IL-6 gene promoter (-174 C/G) and were classified as C allele carriers (C+) and non-carriers (C-). We found that: (i) the interindividual difference in in vitro IL-6 production was wider in elderly individuals in respect to young individuals, leading to different coefficient of variation in the two groups; (ii) the -174 C/G polymorphism had an age-related effect on IL-6 in vitro production. Only among C- people, cells from elderly subjects produced significant higher level of IL-6 than cells from young subjects. These data are consistent with our previous results regarding the IL-6 serum levels in a large group of people of different age, including centenarians. Thus, the EBV-immortalized B lymphocytes can be considered a useful in vitro model for studying the genetic control of IL-6 production and its changes with age.     

乙型肝炎病毒宫内感染与IFN-γ和IL-4、IL-6细胞因子的相关性

目的研究乙型肝炎病毒宫内感染与白细胞介素-4(IL-4)、白细胞介素-6(IL-6)和干扰素-γ(IFN-γ)细胞因子的相关性。方法将研究对象分为两组:研究组为80例乙型肝炎病毒表面抗原(HBsAg)阳性孕妇;对照组为20例正常孕妇。采用双抗夹心酶联免疫吸附法(DAS-ELISA)检测孕妇外周静脉血及其新生儿脐静脉血血清中乙型肝炎五项指标及细胞因子IFN-γ、IL-4、IL-6水平。结果研究组孕妇分娩的新生儿80例有11例宫内感染,宫内感染率为13.75%。新生儿HBV宫内感染组孕妇血清中IFN-γ水平显著低于HBV宫内未感染组及对照组孕妇(P<0.01),IL-4、IL-6水平则显著高于HBV宫内未感染组及对照组孕妇均有统计学意义(P<0.01)。HBV宫内未感染组与对照组相比,上述三种细胞因子水平差异均无统计学意义(P>0.05)。上述各组孕妇血清中IL-4与IL-6水平均呈显著正相关(P<0.01,P<0.01,P<0.01);IFN-γ与IL-4呈显著负相关(P<0.01,P<0.01,P<0.01);IFN-γ与IL-6亦呈显著负相关(P<0.01,P<0.01,P<0.01)。各组新生儿脐血清中IFN-γ、IL-4、IL-6水平差异无统计学意义(P>0.05)。结论孕妇细胞免疫功能紊乱导致IFN-γ抗病毒作用减弱,IL-4、IL-6水平升高,不利于孕妇体内HBV清除,易导致胎儿宫内感染。     

Association between hepatitis B virus infection and HLA-DRB1 genotyping in Shaanxi Han patients in northwestern China

Hepatitis B virus (HBV) infection is a major public health problem worldwide. The mechanism of susceptibility to chronic persistent HBV infection is not well clarified, while the outcome of HBV infection mainly depends on the host immune response. Human leukocyte antigen (HLA) class II molecule is an integral component of the immune response on which majority of host genetic studies have concentrated. Many different HLA class II alleles have been demonstrated to play roles in HBV infection. In this study, the association between HBV infection and HLA-DRB1 alleles in Han individuals in northwestern China was studied for the first time. Two hundred and fifty Shaanxi Han individuals were categorized into three different groups: the HBV-infected patient group (n = 108), the spontaneously cleared control group (n = 108) and the unexposed group (n = 34). DRB1*04, DRB1*09, DRB1*12 and DRB1*15 were the most common genotypes in all the groups. The allele frequencies of HLA-DRB1*03 [10.6% of HBV-infected patients vs 3.7% of spontaneously cleared controls, odds ratios (OR) = 3.10, Pc = 0.008, P < 0.05] and HLA-DRB1*07 (17.6% of HBV-infected patients vs 9.3% of spontaneously cleared controls, Pc = 0.016, OR = 2.09, P < 0.05) were markedly higher in the HBV-infected group. But the allele frequencies of HLA-DRB1*15 (6.9% of HBV-infected patients vs 13.4% of spontaneously cleared controls Pc = 0.039, OR = 0.48, P < 0.05) were obviously lower than that of the spontaneously cleared controls. The above data indicate that HLA-DRB1*03 and HLA-DRB1*07 are related to susceptibility to chronic HBV infection, and DRB1*15 is negatively related to persistence to chronic HBV infection among people in northwestern China. Similar results were got for DRB1*03 and 15 alleles between the HBV-infected patients (n = 108) and 46 HBV seronegative spouses of the HBV patients, who were high-risk group for HBV infection. The above results suggest that host HLA class II gene is an important factor in determination of the outcome of HBV infection.     

胎盘组织TLR9分布与表达及与HBV宫内感染的关系

目的了解TLR9在外周血HBsAg阳性母亲胎盘组织中的表达及分布,探讨其与HBV宫内感染的关系。方法Abbott化学发光法检测新生儿外周血HBsAg;ELISA法检测母亲外周血HBV标志物;SABC免疫组织化学方法检测胎盘组织HBsAg和TLR9的表达和分布。结果胎盘HBV感染率77.27%(17/22),HBsAg分布于蜕膜细胞、滋养层细胞、间质细胞、绒毛毛细血管内皮细胞。TLR9在外周血HBsAg阴性母亲胎盘滋养层细胞表达,在外周血HBsAg阳性母亲胎盘滋养层细胞、间质细胞、绒毛毛细血管内皮细胞均有表达。外周血HBsAg阳性组比阴性组胎盘组织TLR9表达强,差异有统计学意义(P<0.05);而外周血HBsAg阳性母亲的胎盘,未感染HBV者比感染HBV者TLR9表达强,差异有统计学意义(P<0.05)。结论初步认为,胎盘组织TLR9表达与HBV宫内感染有一定关系,TLR9可能是HBV宫内感染的保护因素之一。     

慢性乙型肝炎患者血清和肝组织中HBV DNA含量与庚型肝炎病毒感染的关系

目的：观察慢性乙型肝炎（CH－B）患者血清、肝组织中HBV DNA含量与庚型肝炎病毒（HGV）感染的关系，探讨HGV感染对CH－B患者乙型肝炎病毒（HBV）复制的影响。方法：应用逆转录－聚合酶链反应（RT－PCR）、免疫组织化学法、荧光定量PCR（FQ－PCR）技术方法对56份CH－B患者血清HGV RNA、肝组织HGV Ag、血清及肝组织中HBV DNA含量分别进行了检测，并将血清HGV RNA与肝组织HGV Ag的表达、HGV RNA、HGV Ag阳性与阴性患者HBV DNA含量分别进行了对比研究。结果：血清HGV RNA、肝组织HGV Ag阳性分别为10份（17．9％）、8份（14．3％）。血清HGV RNA阳性与肝组织HGV Ag表达显著相关（P＜0．01），但部分肝组织HGV Ag阴性患者亦有血清HGV RNA表达。血清HGV RNA、肝组织HGV Ag阳性与阴性患者血清及肝组织中HBV DNA含量差异无显著性（P＞0．05）。结论：HGV感染对CH－B患者HBV复制无影响。HGV可在肝脏中复制，但致病性可能较微弱。     

Genetic association of polymorphisms at the intergenic region between PRDM1 and ATG5 with hepatitis B virus infection in Han Chinese patients

Chronic hepatitis B virus (HBV) infection is related to chronic hepatitis, cirrhosis, and hepatocellular carcinoma (HCC), and the interplay between the virus and host immune response leads to different outcomes of the infection. PR domain zinc finger protein 1 (PRDM1) and autophagy-related protein 5 (ATG5) are involved in immune response and HBV infection. An intergenic region between PRDM1 and ATG5 (PRDM1-ATG5 region) has been identified, and single-nucleotide polymorphisms (SNPs) in this region were shown to be involved in immune regulation. This study investigated the functionally relevant rs548234, rs6937876, and rs6568431 polymorphisms at the PRDM1-ATG5 region in a Han Chinese population (403 patients with chronic HBV infection [171 chronic hepatitis, 119 cirrhosis, and 113 HCC], 70 infection resolvers, and 196 healthy controls). The frequencies of the rs6568431 allele A in HBV patients (P = .005) and genotype CA in infection resolvers (P = .005) were significantly higher than in healthy controls. In the dominant model, HCC patients had significantly higher frequencies of rs548234 genotypes CC + TC than cirrhosis patients (P = .009). Rs548234 was an independent factor for HCC in comparison with either cirrhosis (P = .005) or all chronic HBV infection without HCC (P = .018). Functional annotation showed evidence of the role of the SNPs in gene regulation. In conclusion, through this study it is revealed for the first time that rs6568431 may be associated with susceptibility to HBV infection and that rs548234 may be associated with HCC risk in chronic HBV infection, supporting the presence of HBV-related disease-causing regulatory polymorphisms in the PRDM1-ATG5 intergenic region.     

Association of polymorphism in MicroRNA 219‐1 with clearance of hepatitis B virus infection

Polymorphisms in the primary microRNA region may be associated with natural course of hepatitis B virus (HBV) infection. This study evaluated if the mircoRNA 219‐1 (miR‐219‐1) polymorphism can influence the susceptibility towards persistence of HBV infection and the progression to hepatocellular carcinoma (HCC) in patients with chronic HBV infection. A total of 1,439 individuals having either past or present evidence of HBV infection were enrolled for the study. The subjects were divided into four groups; (1) spontaneous recovery (n = 404), (2) chronic HBV carrier (n = 313), (3) chronic HBV carrier with cirrhosis (n = 305), and (4) hepatocellular carcinoma (n = 417). Genotyping was performed at three polymorphic variants (rs421446, rs107822, and rs213210) in the pri‐miRNA region of miR‐219‐1. The rs421446 T allele was found to be strongly associated with HBV clearance (OR = 0.73, P = 0.0005 in a codominant model and OR = 0.67, P = 0.0009 in a dominant model, OR = 0.69, P = 0.04 in a recessive model, respectively). The rs107822 G allele was also found to be associated with HBV clearance (OR = 0.79, P = 0.008 in a codominant model and OR = 0.72, P = 0.01 in a dominant model, respectively). In haplotype analysis, ht2 (T‐G‐T) and ht1 (C‐A‐C) were found to be in significant association with the clearance of HBV. However, no significant association was observed between miR‐219‐1 polymorphism and the risk of HCC occurrence. This result suggests that polymorphisms in the pri‐miRNA region of miR‐219‐1 might be a genetic factor for HBV clearance after infection. J. Med. Virol. 85:808–814, 2013. © 2013 Wiley Periodicals, Inc.