宿主基因多态性与结核易感性研究进展

单核苷酸多态性是人类基因多态性的一类,被认为是新一代遗传标记;越来越多的单核苷酸多态性被报道与特定疾病、特定地区的高危发病人群和易感的患病个体具有相关性;宿主遗传因素在结核病的发生发展中起着重要作用;研究发现单核苷酸多态性可能影响机体对结核病的免疫力,造成机体对结核病易感性发生改变;该综述针对既往研究中关于结核病易感基因的特点和相关调控机制进行回顾分析,对宿主基因多态性与结核易感性之间的研究进展作一综述。     

哮喘的遗传学研究进展

哮喘是一种常见的多基因复杂性疾病,具有较高的遗传度。近年来,寻找哮喘的易感基因已成为哮喘遗传学研究的主要内容。本文对定位克隆、候选基因研究和全基因组关联研究等寻找哮喘易感基因的策略,及近年来研究较多的一些哮喘易感基因的研究进行简要概述。     

患病风险——抵抗力下降，结核“乘虚而入”

最主要因素：抵抗力下降结核病的流行包括3个环节：传染源、传播途径和易感人群。结核病的主要传染源是排菌的肺结核病人．传播途径主要是呼吸道传播．易感人群为从未感染过结核杆菌的人。     

2型糖尿病易感基因单核甘酸多态性的研究进展

2型糖尿病是多基因复杂病,具有高度遗传异质性,不同地区、不同种族人群的遗传背景不同,参与2型糖尿病发生的易感基因也不同。近年来单核苷酸多态性与2型糖尿病发病相关性研究的取得了一定的进展,但尚未发现任何一个SNP在所有人群中均与2型糖尿病相关联。本文拟就2型糖尿病相关易感基因单核苷酸多态性及其发病机制研究进展进行综述。     

多囊卵巢综合征遗传学研究新进展

多囊卵巢综合征(PCOS)是一种复杂的生殖内分泌疾病,主要特征是月经稀发或闭经、高雄激素血症以及卵巢多囊样改变。遗传因素在PCOS发病中的重要作用已经得到证实,许多候选基因也被识别。目前发现的易感基因主要包括参与甾体激素生物合成、转运、作用和调节的相关基因,慢性炎症相关基因,胰岛素抵抗和转化生长因子β(TGF-β)通路相关基因等。全基因组关联研究(genome-wide association study,GWAS)为了解PCOS的发病机制提供了新方向。然而,由于PCOS患者基因和表型复杂,目前遗传学研究仍未得出明确结论。现对PCOS遗传学研究最新进展进行综述。     

遗传易感因素与慢性乙型肝炎干扰素治疗反应的相关性

IFN-α以抗病毒及免疫调节双莺作用用于慢性乙型肝炎的治疗,对治疗反应的早期预测有利于治疗的持续.随着人类基因组学和蛋白质组学的研究进展,国内外对HBV感染发病及治疗反应遗传易感因素有较多报道,主要集中于抗病毒蛋白和免疫调节相关细胞因子的基因多态性.此文就遗传易感因素对IFN-α治疗慢性乙型肝炎疗效的影响作了综述.     

基因与环境对儿童健康的影响

由于人群在生物学方面是多样性的，在遗传学方面是异源性的，所以在接触或未接触环境有害物质的个体中间对疾病存在不同的易感性，并不奇怪。不同个体对疾病的易感性可能有很大差异，成年人和儿童都如此。许多儿童期疾病是在发育的易感时期遗传感染性与环境接触等因素共同作用的结果。基因调节细胞的生长发育、ＤＮＡ的复制和修复、机体内内源性物质的代谢以及来自环境接触的外源性物质的代谢。基因的这种调节作用有人的一生中是有所     

肠道病毒71型感染相关遗传易感基因研究现状

肠道病毒71型(EV71)是引起婴幼儿手足口病(HFMD)的最常见肠道病毒之一。EV71侵染取决于病毒、宿主及环境的多重作用,特别是介导EV71病毒与宿主固有免疫及适应性免疫反应功能异常相关基因的多态性与EV71易感关系密切。在此过程中,越来越多白细胞介素类(IL-4,IL-8,IL-17F和IL-18)、趋化因子类(MCP-1,IP-10)及抗病毒蛋白类(OAS,HLA)相关基因被筛选发现与EV71易感及病程恶化密切相关。本文就近年来EV71感染相关遗传易感基因筛选研究状况作一综述。     

HLA-B基因多态性与严重急性呼吸综合征冠状病毒易感性关系研究

目的研究HLA-B基因多态性与严重急性呼吸综合征冠状病毒(SARS-CoV)易感性的关系,以揭示遗传因素在严重急性呼吸综合征(SARS)发病中的作用。方法采用病例-对照的研究设计,运用PCR-SBT方法,对43例SARS康复后病人、30例高危医护人员对照和62例健康对照的HLA-B位点等位基因型分布进行研究,并根据基因型指定血清型进行分析。运用SPSS11.5软件包进行统计分析,组间比较采用χ2检验,计算比值比(OR)及其95%可信区间(95%CI)。结果与健康人群比较,SARS康复病人HLA-B*51G1和HLA-B*5502基因型以较低频率出现,但两者差异无统计学意义(P=0.08)。同时,与高危人群比较,SARS康复病人HLA-B*51G1基因型出现频率较低,差异也无统计学意义(P=0.07),而HLA-B*130201和HLA-B*5801基因型以较高频率出现(P值分别为0.08和0.08)。血清型结果显示HLA-B血清型B13(P=0.03,OR=4.73,95%CI1.01～21.85)和B35(P=0.04,由于HCW该血清型为0,OR不能计算)为SARS-CoV感染的易感因素,而B07(P=0.01,OR=0.16,95%CI0.03～0.76)、B27(P=0.01,OR=0.16,95%CI0.03～0.76)和B49(P=0.01,由于SARS病人该血清型为0,OR不能计算)为SARS-CoV感染的保护因素。结论HLA-B*51G1和5502基因型可能在SARS发生中起到保护作用,而HLA-B*130201和5801基因型可能是SARS发生的易感因素。而按照血清分型,B13和B35为SARS-CoV感染的易感因素,B07、B27和B49为SARS-CoV感染的保护因素。     

eNOS基因在妊娠高血压综合征中的作用

妊娠高血压综合征是产科常见的并发症 ,是引起孕产妇和围产儿死亡的主要原因之一。其发病原因和发病机理目前尚不清楚 ,近年来越来越多的证据表明 ,妊高征与遗传学因素有着密切关系 ,与无妊高征家族史的妇女相比 ,一级亲属的发病率约为一般的 5倍。一氧化氮是重要的血管紧张性调节分子 ,一氧化氮合酶是一氧化氮产生的重要限速酶 ,其中内皮型一氧化氮合酶是与妊高征关系密切的酶 ,研究表明eNOS在妊高征的发病机理中有重要的作用。提示它是妊高征重要的易感基因。国外对在此领域进行了一些研究 ,但仍存在争议。现就eNOS的基因在妊娠高血压综合征中的作用进行阐述。     

Genetic susceptibility to Tuberculosis: Interaction between HLA-DQA1 and age of onset

Several genome-wide association studies (GWAS) identified new single nucleotide polymorphisms (SNPs) with susceptibility to Tuberculosis (TB). However, many of them were not replicated across ethnic groups. The cause of this phenomenon of genetic heterogeneity is uncertain. Here, we attempted to replicate and evaluate the mechanism that causes genetic heterogeneity in several putative TB predisposition loci found by previous GWAS, including chromosome 18q, ASAP1, DUSP14, and HLA-DQA1. A Chinese cohort of 1200 TB patients and 1280 population controls were genotyped. The results showed that genetic predisposition to TB might operate in an age-specific manner. While no significant association was found in the whole samples, a SNP of HLA-DQA1, rs9272785, showed suggestive association within the young-onset TB subgroup (onset at 20–40 years of age, N = 396). The results provide support for the hypothesis that there are different pathogenesis mechanisms causing clinical TB disease in different age groups, and that genetics probably play a substantial role only in young-onset TB.     

艾滋病与结核病患者双重感染检出率及其影响因素的调查

[目的]了解广西艾滋病人中结核病患病率,结核病患者中HIV感染检出率;调查广西艾滋病患者发生结核病及结核病患者感染HIV的影响因素。[方法]对260例艾滋病患者及580例结核病患者进行双重感染检出率及其影响因素的问卷调查,并查看病例。[结果]260例HIV/AIDS患者中结核病患病率为35.0%（肺结核为29.2%,肺外结核为5.8%）,580例结核病患者HIV感染检出率为2.8%;影响260例艾滋病患者发生结核病的主要影响因素为月收入,影响580例结核病患者感染HIV的主要影响因素为吸毒和商业性行为。[结论]艾滋病患者发生结核病的机率高,月收入低者易发生结核病;结核病患者中HIV感染检出率高于一般人群,吸毒和商业性行为是结核病患者感染HIV的主要途径。     

The burden of tuberculosis in indigenous peoples in Amazonia, Brazil

Tuberculosis (TB) stands out as one of the principal infectious diseases affecting Amazonian Indians. Recent research indicates that incidence rates among indigenous peoples may be as much as ten times higher than those of the general Brazilian population. Purified protein derivative reactivity in Amazonia is low compared with populations of European descent; anergy rates usually surpass 50%, even under high BCG coverage. An annual risk of infection of 1.2-2.2% points to high rates of transmission. Whether or not particular susceptibility to TB is linked to genetics, Amazonian Indians face a disproportionately high risk of contracting and dying from TB.     

Sp110基因rs1135791、rs722555多态性与结核病的相关性研究

[目的]研究Sp110基因rs1135791、rs722555多态性与肺结核易感性的关系。[方法]采用病例对照研究，选取重庆地区100例肺结核患者和106例健康对照，运用嵌套式等位基固特异性引物PCR技术检测Sp110基因rs1135791C／T位点和rs722555A／G位点基因型，运用X＾2检验分析其基因型频率和等位基因频率与肺结核的相关性。[结果]病例组rs1135791CT基因型、C等位基因频率均高于对照组．差异有统计学意义（P〈0．05），OR值分别为1．9795和1．6951；病例组rs722555GG基因型、G等位基因颊率均高于对照组，差异有统计学意义（P〈0．05）、DR值分别为2．0235和1．5874。[结论]Sp110基因rs1135791、rs722555多态性可能是重庆地区汉族人群肺结核遗传易感性的危险因素。     

Eosinophilia and progression to active tuberculosis in HIV-1-infected Ugandans

It has been suggested that type 1 immune responses protect against tuberculosis (TB), while type 2 responses, such as those induced by helminths, may suppress protective responses and increase susceptibility to TB. Factors associated with progression to active TB were investigated in a cohort of HIV-1-infected Ugandan adults, a group at high risk of TB. High rates of subsequent progression to active TB were associated with eosinophil counts > or = 0.4 x 10(9)/L at enrolment. Eosinophilia at enrolment was associated with male gender, low socio-economic status, high CD4+ T cell counts, and schistosomiasis, but adjusting for these factors did not explain the association of eosinophilia with progression to active TB (adjusted rate ratio = 2.76, P = 0.004). Eosinophilia is most likely to be indicative of a type 2 immune response induced by helminth infection in this Ugandan cohort, but the mechanism of the observed association between eosinophilia and risk of TB remains to be determined.     

Polymorphisms in SP110 are not associated with pulmonary tuberculosis in Indonesians

Despite being high transmissible, Mycobacterium tuberculosis (M. tuberculosis) infection causes active disease in only 5-10% of disease-susceptible individuals. This has instigated interest in studying potentially underlying genetic host factors and mechanisms in tuberculosis (TB). The recent identification of the Intracellular pathogen resistance 1 (Ipr1) gene, which plays a major role in controlling M. tuberculosis susceptibility and infection severity in mice (Pan et al., 2005), has prompted studies on its human homolog; SP110 in humans. Association of SP110 SNPs with pulmonary TB were first reported in a study on West African families (Tosh et al., 2006). Subsequent attempts to replicate these findings in other populations, including another West African (Ghanaian) cohort (Thye et al., 2006), however, were unsuccessful. Here we have genotyped 20 SNPs located in the SP110 gene, including the previously TB associated variants; rs2114592 and rs3948464, for the first time in a South East Asian cohort from Indonesia. Our study did not reveal any statistically significant associations between SP110 SNPs and pulmonary TB. In addition, a meta-analysis of the two previously TB associated SNPs revealed that these are not associated with TB, further confirming the lack of convincing evidence for SP110 to be implicated in TB susceptibility, as yet in humans.     

NRAMP1基因INT4和3’UTR位点多态性与肺结核易感性的研究

目的 探讨人类自然抵抗相关巨噬细胞蛋白1（NRAMP1）基因INT4和3＇UTR位点多态性与中国北方汉族成人肺结核发病的关系.方法 采用1：1配对的病例对照研究设计,用聚合酶链反应-限制性片段长度多态性分析方法检测NRAMP1基因中INT4和3＇UTR两个多态性位点,对与肺结核相关的危险因素进行问卷调查,进行单因素和多因素条件logistic回归分析,同时对基因型与肺结核病变的性质和程度进行研究.结果 对124对研究对象进行了INT4和3＇UTR两个多态性位点的基因分型,3＇UTR TGTG＋/del基因型病例组频率显著高于对照组,粗OR值（95%CI）为2.923（1.557～5.487）.病例组和对照组INT4各基因型频率比较差异均无统计学意义.对17个环境危险因素进行了单因素分析,在多因素分析中调整卡痕、体重指数、人均居住面积、家族史4个因素后,3＇UTR TGTG＋/del基因型仍与肺结核显著相关,调整OR值（95%CI）为2.955（1.369～6.381）.在INT4不同基因型中,病例组和对照组肺结核病变性质差异具有统计学意义（x2=9.634,P＜0.05）.结论 NRAMP1基因3＇UTR位点多态性可能是中国北方汉族成人肺结核的易感因素,而INT4多态性可能与肺结核的病变性质有关系.     

2型糖尿病的危险因素及干预综述

糖尿病是危害人类健康的疾病,2型糖尿病的发生是遗传因素和生活方式与行为因素共同作用的结果,遗传因素决定了个体对糖尿病的易感性,而不同的生活方式与行为因素可能是诱发糖尿病发生的外部原因;糖尿病所导致的严重并发症已给社会经济造成巨大负担,防止并发症是糖尿病治疗的目的,系统的心理行为干预对于糖尿病的防治起着举足轻重的作用。     

A susceptibility locus for radiation lymphomagenesis on mouse chromosome 16

BALB/cHeA (BALB/c) mice are sensitive to radiation lymphomagenesis, while STS/A (STS) mice are resistant. We have selected a recombinant mouse, R1, with a STS-derived D16Mit165-D16Mit34 segment in the vicinity of the centromere of chromosome 16 among progeny from a (CcS-7/Dem x BALB/c)F1 x BALB/c backcross. To test the susceptibility to radiation lymphomagenesis, we generated a genetic cross by mating the male and female R1 progeny obtained by 4-6 backcrosses of R1 to BALB/c. The mice were subjected to 4 x 1.7 Gy of X-irradiation. Of 120 mice analyzed, 94 developed lymphomas (91, of thymic type; 3, of nonthymic type) within 315 days of observation. The analysis indicated a link between the susceptibility to lymphomagenesis and the marker D16Mit34 on chromosome 16. The mice heterozygous for the BALB/c and STS alleles at D16Mit34 were less sensitive to lymphomagenesis than the mice homozygous at this locus. There was no significant difference in latency among the genotypes. Our study showed the existence of a susceptibility locus for radiation lymphomagenesis on chromosome 16 and revealed aspects of the genetics of lymphoma susceptibility.     

Recombinant Ag85B vaccine by taking advantage of characteristics of human parainfluenza type 2 virus vector showed Mycobacteria-specific immune responses by intranasal immunization

Viral vectors are promising vaccine candidates for eliciting suitable Ag-specific immune response. Since Mycobacterium tuberculosis (Mtb) normally enters hosts via the mucosal surface of the lung, the best defense against Mtb is mucosal vaccines that are capable of inducing both systemic and mucosal immunity. Although Mycobacterium bovis bacille Calmette-Guérin is the only licensed tuberculosis (TB) vaccine, its efficacy against adult pulmonary forms of TB is variable. In this study, we assessed the effectiveness of a novel mucosal TB vaccine using recombinant human parainfluenza type 2 virus (rhPIV2) as a vaccine vector in BALB/c mice. Replication-incompetent rhPIV2 (M gene-eliminated) expressing Ag85B (rhPIV2–Ag85B) was constructed by reverse genetics technology. Intranasal administration of rhPIV2–Ag85B induced Mtb-specific immune responses, and the vaccinated mice showed a substantial reduction in the number of CFU of Mtb in lungs and spleens. Unlike other viral vaccine vectors, the immune responses against Ag85B induced by rhPIV2–Ag85B immunization had an advantage over that against the viral vector. In addition, it was revealed that rhPIV2–Ag85B in itself has an adjuvant activity through the retinoic acid-inducible gene I receptor. These findings provide further evidence for the possibility of rhPIV2–Ag85B as a novel TB vaccine.