TGF-β1基因T29→C多态性与2型糖尿病肾病的相关性

应用PCR-RFLP技术检测福建地区167例2型糖尿病患者（其中80例合并糖尿病肾病）和62名健康对照者TGF-β1基因T29→C多态性,结果显示,C等位基因可能与糖尿病肾病发病相关。     

高海拔区汉、藏、回族原发性高血压与载脂蛋白E基因多态性的相关研究

目的:检测载脂蛋白E(ApoE)基因多态性并探讨其与高海拔区汉、藏、回族原发性高血压之间的关系。方法:汉族高血压病组67例,对照组64例;藏族高血压病组67例,对照组53例;回族高血压病组48例,对照组52例;对各族进行血压测量,采集静脉血,提取DNA,以聚合酶链反应—限制性片段长度多态性方法(PCR-RFLP)进行DNA多态性分析,电泳判断基因型。结果:ApoE基因构成比在汉族高血压病组与对照组之间差异有统计学意义(P<0.05),而在藏族高血压病组与对照组之间有极显著性差异(P<0.01),在藏族高血压病组E4等位基因频率高于对照组,而E2等位基因频率低于对照组(P<0.01),回族高血压病组各基因型分布和等位基因频率与对照组无差异(P>0.05)。结论:高海拔区藏、汉族人群中,ApoE基因E4等位基因与原发性高血压相关,回族无此相关性。     

江苏汉族人群p53第7内含子多态性与慢性萎缩性胃炎无相关性

目的:探讨江苏汉族人群p53第7内含子多态性与慢性萎缩性胃炎(CAG)之间的相关性.方法:提取80例CAG患者、76例健康体检人群基因组DNA,PCR特异性扩增p53基因第7,8外显子及其间的第7内含子,产物纯化后测序,将样品序列与标准序列进行比对,观察第7内舍子多态性.组间的基因型及等位基因频率比较采用χ~2检验.结果:CAG组p53基因第7内含子的第72位碱基和第92位碱基等位基因分别为T-G (32.5%)和C-T(67.5%),基因型表现为T-G/T-G (11.3%),C-T/T-G(42.5%)和C-T/C-T(46.3%)3种;在体检组中相应的等位基因T-G和C-T的频率是29.6%和70.4%,3种基因型频率分布分别为9.2%(T-G/T-G),40.8%(C-T/T-G)和50.0%(C-T/C-T).等位基因频率和基因型分布在CAG组和体检组差异无统计学意义(P>0.05),T-G等位基因携带者和C-T等位基因携带者患CAG的危险性差异无统计学意义(OR=1.14).结论:江苏汉族人群p53第7内含子多态性与CAG表遗传外显率无直接致病关系.     

DNA repair gene XRCC1 and XPD polymorphisms and their association with coronary artery disease risks and micronucleus frequency

Coronary artery disease (CAD) is a multifactorial process that appears to be caused by the interaction of environmental risk factors with multiple predisposing genes. In this study, we investigated the effects of the XPD Lys751Gln and XRCC1 Arg399Gln polymorphisms on the presence and the severity of CAD. We also investigated the presence of DNA damage in the peripheral lymphocytes of patients with CAD by using the micronucleus (MN) test and the effect of XPD Lys751Gln and XRCC1 Arg399Gln polymorphisms on this damage. The study population consisted of 147 patients with angiographically documented CAD and 48 healthy controls. No association between XPD Lys751Gln or XRCC1 Arg399Gln polymorphisms and the presence or the severity of CAD was observed. On the other hand, a significantly higher frequency of MN was observed in CAD patients compared with controls (5.7 ± 1.9 vs 5.0 ± 2.1, respectively, P = 0.018). We found an elevated frequency of MN in CAD patients with the XPD 751Gln allele (Gln/Gln genotype) or the XRCC1 399Gln (Arg/Gln or Gln/Gln genotypes) allele compared with the XPD 751Lys (Lys/Lys genotype) allele or XRCC1 399 Arg (Arg /Arg genotype) allele, respectively. These preliminary results suggest that XPD Lys751Gln and XRCC1 Arg399Gln polymorphisms may not be a significant risk factor for developing CAD. In addition, our results indicate that the MN frequency is associated with presence, but not severity, of CAD and is related to the XRCC1 Arg399Gln and XPD Lys751Gln polymorphisms, suggesting an elevated frequency of MN in CAD patients with the XPD 751Gln or XRCC1 399Gln alleles.     

CCL2-2518 A/G and CCR2 190 A/G do not influence the outcome of hepatitis C virus infection in the Spanish population

AIM： To assess whether CCL2 or interactions between this chemokine and its receptor （CCR2） are associated with outcomes of chronic hepatitis C and with responses to antiviral therapy.
METHODS： Two hundred and eighty-four patients with chronic hepatitis C and 193 non-infected matched controls were included in this study. Patients were categorized according to their Scheuer score of hepatic fibrosis as F0-F2 （/7 = 202） or F3-F4 （/7 = 82） and according to their response to anti-Hepatitis C virus （HCV） therapy as sustained response （SR, n = 201） or non-sustained response （NSR, n = 98）. Genotyping of the -2518 （A/G） CCL2 was performed using PCR-RFLP, genotyping of the 190 （A/G） CCR2 using a PCR-ARMS system, and genotyping of the rs3138042 （G/A） CCR2 using Taqman probes.
RESULTS： Univariate analyses identified 4 parameters （infection duration time, viral genotype, gender and AST levels） that tended to influence fibrosis and 7 parameters （CCL2G, CCL2ACCR2A, viremia levels, fibrosis stage, viral genotype, infection duration time and AST levels） that significantly influenced or tended to influence response to treatment. Multivariate analysis identified gender and AST levels as parameters that independently influenced fibrosis stage and viral genotype and infection duration time were the two parameters that independently influenced response to treatment.
CONCLUSION： Our results indicate that the mutations studied in the gene pair CCL2/CCR2 do not play a major role in the outcome and response to treatment for HCV infection in the Spanish population.     

树突状细胞表面特异性非整联蛋白外显子4在中国裔丙型肝炎患者中的遗传多态性

目的探讨树突状细胞表面特异性非整联蛋白（DC—SIGN）及其同源物（DC-SIGNR）外显子4遗传多态性在中国裔丙型肝炎患者中是否存在遗传易感性。方法采用PCR结合DNA测序对300例丙型肝炎患者和520名健康人的DC-SIGN和DC-SIGNR外显子4重复序列多态性进行基因分型和测序分析。结果DC—SIGN外显子4基因型与等位基因频率在丙型肝炎患者和健康人群间差异无统计学意义（P〉0．05）。DC-SIGNR外显子4等位基因的频率差异也无统计学意义（P〉0．05）；但9／5基因型分布频率在丙型肝炎患者和健康人群间的差异有统计学意义（P〈0．05）。结论DC-SIGN外显子4遗传多态性与HCV感染易感性无明显相关性；9／5基因型DC-SIGNR外显子4在丙型肝炎患者中的分布频率较高，可能与HCV感染的易感性相关，值得进一步研究。     

血管紧张素原基因M235T和T174M多态性与新疆哈萨克族高血压左室肥厚的关系

目的:探讨新疆哈萨克族原发性高血压(EH)人群中血管紧张素原(AGT)基因M235T和T174M多态性的分布及其与EH伴左室肥厚(LVH)的关系。方法:对86例心电图诊断的EH伴LVH患者(LVH组)与95例不伴LVH患者(NLVH组)进行病例-对照研究,即记录标准12导联以传统的电压诊断标准与Romhilt计分系统积分作为诊断LVH的指标。采用聚合酶链式反应(PCR)与限制性片段长度多态性(RFLP)技术检测AGT基因M235T变异及T174M变异。结果:①M235T基因型有2种形式,T174M基因型有3种形式;2组AGT基因型的分布均符合Hardy-Weinberg平衡;②AGT基因M235T和T174M基因型及等位基因在LVH组与NLVH组的分布均差异无统计学意义(均P>0·05);③按性别分层,M235T基因型和等位基因频率在2组男女之间均差异无统计学意义(均P>0·05);T174M基因型和等位基因频率在LVH组男女之间亦均差异无统计学意义(均P>0·05),而在NLVH组男女之间差异有统计学意义(均P<0·05);④AGT基因M235T,T174M位点不同组合基因型在2组人群的构成不存在显著性差异(P>0·05)。结论:AGT基因M235T及T174M多态性与新疆哈萨克族EH伴LVH的发生无相关性。AGT基因M235T及T174M多态性可能不是新疆哈萨克族EH伴LVH的遗传危险因素。     

The relationship between <Emphasis Type="Italic">ACE</Emphasis> genotype and risk of severe hypoglycaemia in a large population-based cohort of children and adolescents with type 1 diabetes

Aims/hypothesis Genetic factors may account for familial clustering related to diabetes complications. Studies have shown a significant relationship between the presence of the deletion (D) allele of the gene encoding ACE and risk of severe hypoglycaemia. This large prospective cohort study assesses this relationship in a large sample of children and adolescents with type 1 diabetes. Subjects and methods We studied 585 children and adolescents (mean age 11.9 ± 4 years, 48.4% males). The frequency of severe hypoglycaemia (an event leading to loss of consciousness or seizure) was prospectively assessed over the 13-year period 1992–2004. Patients were seen with their parents every 3 months and data recorded at each visit. The ACE gene was detected using PCR. Results In our cohort of 585 children, 186 (31.8%) had at least one episode of severe hypoglycaemia, and of these 28.0% had the II genotype, 48.9% had the ID genotype and 23.1% had the DD genotype. This was in agreement with the Hardy–Weinberg proportion. A total of 477 severe hypoglycaemic episodes was recorded with a total of 3,404 person-years of follow-up, giving a total incidence of 14 per 100 patient-years. No significant increase in risk for DD genotype (incidence rate ratio = 0.97, 95% CI 0.61–1.55) relative to II genotype was observed. Conclusions/interpretation This large prospective study concludes that the presence of the D allele of the ACE gene does not predict a significantly higher risk of severe hypoglycaemia in type 1 diabetic children and adolescents.     

Polymorphisms of the methylenetetrahydrofolate reductase gene and clinical outcomes in HLA-matched sibling allogeneic hematopoietic stem cell transplantation

To evaluate whether the C677T and A1298C polymorphisms of 5,10-methylenetetrahydrofolate reductase (MTHFR) are related to the toxicity of methotrexate (MTX) used in allogeneic stem cell transplantation, we performed association analysis between these genetic polymorphisms and the clinical outcomes of patients treated using human leukocyte antigen-matched sibling stem cell transplantation. Patients (n=72) with hematological malignancy or aplastic anemia were given a short course of MTX as a graft-versus-host disease prophylaxis. Patients with the 677TT genotype showed higher total bilirubin levels (677TT vs 677CT vs 677CC, 14.5 vs 8.6 vs 3.8 mg/dl, respectively; p=0.07) and higher aspartic transaminase levels (677TT vs 677CT vs 677CC, 678.9 vs 156.6 vs 111.8 IU/l; p=0.04). Platelet recovery to 20,000/μl was slower for patients with the 677TT genotype than for patients with other genotypes (677TT, 59 days; 677CT, 26 days; 677CC, 26 days; p=0.0075). The influences of the C677T polymorphism on treatment-related mortality (TRM) were also analyzed. One-year cumulative TRMs for patients with the TT genotype and the other genotypes were 66 and 30% (p=0.04) and their respective 1-year overall survivals were 30 and 56% (p=0.11). No association was observed between the A1298C polymorphism and clinical outcome for any of the different genotypes. Therefore, patients at high risk of developing hepatic toxicity and with a poor likelihood of survival could be selected by genotyping MTHFR C677T before allogeneic stem cell transplantation.     

Characterization of B-cell lines from SLE patients and their relatives

Epstein-Barr-virus (EBV)-transformed lymphoblastoid B-cell lines were generated from peripheral blood lymphocytes of 55 patients with systemic lupus erythematosus (SLE) and 44 healthy relatives. All donors have previously been extensively characterized with regard to clinical, serologic, and genetic parameters. Here, peripheral blood lymphocytes and lines were characterized for cell surface antigens. Furthermore, autoantibody production and proliferation rate of the cell lines were monitored. A significant difference between patients and relatives was the lower proliferation rate of EBV-transformed cell lines of the SLE patients. All SLE cell lines are available for interested researches and can be obtained from the European Cell Bank, Salisbury, UK.