早老素-1基因启动子区-48C/T位点多态性与LOAD的遗传相关性

目的研究早老素-1基因启动子区-48C/T位点的多态性与迟发性AD(LOAD)的相关性.方法用常规方法从人外周血白细胞中抽提基因组DNA,PCR扩增出包含-48C/T多态性位点的基因片段,利用PCR-RFLP技术对-48C/T多态性位点进行基因分型,χ2检验分析-48C/T多态性位点基因型分布和等位基因频率.结果以33例AD病例和32例对照样品的外周血白细胞基因组DNA为模板,PCR扩增出了长度为344bp的包含-48C/T多态性位点的基因片段.基因分型结果表明,33例散发型AD的C和T等位基因频率分别为47%和53%,C/T和T/T基因型频率分别为94%和6%.而32例正常对照的C和T等位基因频率分别为48%和52%,C/T和T/T基因型频率分别为97%和3%.χ2检验结果显示,病例-对照样品间C和T等位基因频率及C/C、C/T和T/T基因型的分布均无显著性差异(χ2值分别为0.443和0.318,P>0.05).结论在我们研究的群体中,早老素-1基因启动子区-48C/T位点的多态性与LOAD无显著的遗传相关性.     

Association between presenilin-1 polymorphism and maternal meiosis II errors in Down syndrome

Several lines of evidence suggest a shared genetic susceptibility to Down syndrome (DS) and Alzheimer disease (AD). Rare forms of autosomal-dominant AD are caused by mutations in the APP and presenilin genes (PS-1 and PS-2). The presenilin proteins have been localized to the nuclear membrane, kinetochores, and centrosomes, suggesting a function in chromosome segregation. A genetic association between a polymorphism in intron 8 of the PS-1 gene and AD has been described in some series, and an increased risk of AD has been reported in mothers of DS probands. We therefore studied 168 probands with free trisomy 21 of known parental and meiotic origin and their parents from a population-based material, by analyzing the intron 8 polymorphism in the PS-1 gene. An increased frequency of allele 1 in mothers with a meiosis II error (70.8%) was found compared with mothers with a meiosis I error (52.7%, P < 0.01), with an excess of the 11 genotype in the meiosis II mothers. The frequency of allele 1 in mothers carrying apolipoprotein E (APOE) epsilon4 allele (68.0%) was higher than in mothers without epsilon4 (52.2%, P < 0.01). We hypothesize that the PS-1 intronic polymorphism might be involved in chromosomal nondisjunction through an influence on the expression level of PS-1 or due to linkage disequilibrium with biologically relevant polymorphisms in or outside the PS-1 gene.     

醛固酮合成酶基因-344T/C多态性与高血压病相关性研究

目的研究醛固酮合成酶基因-344T/C多态性是否与原发性高血压相关.方法多聚酶链反应-限制性片段长度多态性技术检测原发性高血压和对照组醛固酮合成酶基因-344T/C多态性,χ2检验比较各组基因型和等位基因频率.结果对照组TT、TC和CC基因型频率分别为48%、43%和9%,高血压病组TT、TC和CC基因型频率分别为43%、47%和10%;对照组T、C等位基因频率分别为69%和31%,高血压病组T、C等位基因频率分别为66%和34%.经χ2检验两组之间基因型和等位基因频率差异均无显著性(P＞0.05).结论本研究尚不支持醛固酮合成酶基因-344T/C多态性与原发性高血压存在相关性.     

基质金属蛋白酶8-799C/T基因多态性与颈动脉斑块易损性的关联分析

目的 探讨我国浙江地区汉族人群基质金属蛋白酶-8 (matrix metalloproteinase-8,MMP-8)启动子基因-799C/T多态与颈动脉斑块易损性的关系.方法 451例脑梗死患者根据颈动脉超声分为易损斑块组(共135例)和稳定斑块组(共316例).采用酶联免疫吸附法测定两组血清MMP-8水平,并采用聚合酶链反应-限制性片段长度多态性方法分析两组MMP-8启动子基因-799C/T多态的基因型.结果 易损斑块组发病48 h内血清MMP-8水平为(0.86±0.16)ng/μL,稳定斑块组为(0.80±0.13) ng/μL,两者差异有统计学意义(t=2.894,P=0.004).易损斑块组CT+ TT基因型频率为73.3％,稳定斑块组为54.7％,两者差异有统计学意义(x2=13.65,P=0.000);T等位基因频率在易损斑块组为48.1％,在稳定斑块组为33.5％,两者差异有统计学意义(x2=17.14,P=0.000).CC基因型组血清MMP-8水平为(0.79±0.13) ng/μL,TT基因型组血清MMP-8水平为(0.92±0.11) ng/μL,两者比较差异有统计学意义(t=3.141,P=0.001).结论 MMP-8启动子基因-799C/T多态可能与浙江地区汉族人颈动脉易损斑块发生的倾向有关,T等位基因可能是颈动脉斑块易损的遗传易患性标志之一.     

早衰蛋白-1基因内含子多态性与Alzheimer's病的关系

为探讨早衰蛋白－１（ＰＳ－１）基因多态性与Ａｌｚｈｅｉｍｅｒ’ｓ病（ＡＤ０的关系,用聚合酶链反应－限制性片段长度多态性（ＰＣＲ－ＲＦＬＰ）方法检测５１例散发性ＡＤ患者ＰＳ－１外显子８的３‘端内含子基因型,其中４０例晚发性ＡＤ患者,同时检测８７６例健康对照者ＰＳＤ－１基因型。结果发现散发性ＡＤ组１／１基因型和１等位基因频率分别为０．５１０和０．６９６,显著高于对照组的０．２９９和０．５２２;晚发性Ａ     

Association between the interleukin-1beta C(-511)T polymorphism and blood pressure in a Chinese hypertensive population

The interleukin-1beta (IL-1beta) is an important pro-inflammatory cytokine in a broad spectrum of physiological processes. Previous investigations have observed that levels of the IL-1beta were higher in essential hypertensive patients and the IL-1beta gene polymorphism has been shown to be related to IL-1 production. We hypothesized that genetically determined differences in activity or responsiveness of cytokine(s) might contribute to hypertension. In this report, we utilized a family-based design to test the association between the IL-1beta C(-511)T polymorphism and blood pressure levels in hypertensive patients chosen from rural communities in Anhui, China. In men, carriers of the IL-1beta (-511)*C allele were found to have lower systolic (P = 0.049) blood pressure levels compared with T homozygotes, which conforms to an additive effect model. By contrast, no significant association between the IL-1beta gene and blood pressure levels was revealed in women. Our results suggested a significant role of the IL-1beta C(-511)T polymorphism in the control of blood pressure in Chinese hypertensives.     

肿瘤坏死因子α基因启动子区域-1031T/C多态与不稳定性心绞痛的相关性

目的 研究肿瘤坏死因子α(tumor necrosis factor-alpha,TNF-α)基因启动子区域-1031T/C多态与汉族不稳定性心绞痛的相关性.方法 采用MALDI-TOF质谱检测方法,在299例不稳定性心绞痛患者和202名健康对照者中,对TNF-α基因启动子区域的T-1031C多态进行基因分型,并采用酶联免疫吸附实验(enzyme-linked immunosorbent assay,ELISA)法测定其血清浓度.结果 -1031T/C多态的基因型分布及其等位基因频率在两组间相比差异均无统计学意义(P>0.05).但在男性不稳定性心绞痛患者中,其CC、TC和TT基因型分布与对照组相比有统计学意义(P=0.032),男性CC+TC携带者,不稳定性心绞痛的发病危险是TT携带者的1.66倍(95%CI:1.040～2.659).其等位基因频率在两亚组间相比差异无统计学意义(P>0.05).不稳定性心绞痛组的血清TNF-α浓度明显高于对照组(P=0.028,尤其男性亚组P=0.013),TC基因型的血清TNF-α浓度高于其他基因型,但差异无统计学意义(P>0.05).结论 TNF-α基因启动子区域的-1031T/C多态可能与男性不稳定性心绞痛的发生相关,尤其是男性C等位基因携带者.     

CYP11B2基因-344T/C多态性与扩张型心肌病关联研究

目的研究CYP11B2基因4/344T/C多态性是否与汉族人扩张型心肌病关联。方法多聚酶链反应-限制性片段长度多态性技术检测扩张型心肌病和健康对照组CYP11B2基因4/344T/C多态性,χ^2验比较各组基因型和等位基因频率。结果对照组TT、TC与CC基因型频率分别为49%、46%和5%,扩张型心肌病组TT、TC与CC基因型频率分别为49%、44%和7%,经χ^2验两组之间基因型分布差异无显著性（P〉0.05）。对照组T、C等位基因频率分别为72%和28%,扩张型心肌病组T、C等位基因频率分别为71%和29%,经χ^2验两组之间等位基因分布差异亦无显著性（P〉0.05）。结论本研究尚不支持CYP11B2基因4/344T/C多态性与汉族人扩张型心肌病存在关联。     

间隙性连接蛋白37基因1019C/T多态性与经皮冠状动脉介入术后支架内再狭窄的相关性研究

目的 评估无锡地区人群间隙性连接蛋白37(Connexin 37,CX37)基因1019C/T多态性与经皮冠状动脉介入术(percutaneous coronary intervention,PCI)术后支架内再狭窄的相关性.方法 532例PCI术后在我院复查冠脉造影的冠心病患者,按造影结果分为支架内再狭窄组(67例)和无支架内再狭窄组(465例),501名健康人群作为正常对照组,均采用基因测序技术对CX37基因1019C/T多态性位点基因型进行检测,比较3组人群中基因型及等位基因分布差异.结果 (1)在冠心病组与正常对照组比较中,C等位基因及C等位基因携带者(CC+TC)基因型频率冠心病组明显高于正常对照组(C等位基因:57.05％ vs.41.32％,P＜0.01;C等位基因携带者:79.32％ vs.65.47％,P＜0.01);与TT纯合子相比,(CC+TC)基因型冠心病患病风险显著增加(OR=2.03,95％ CI∶1.53～2.80).对性别进行亚组分析显示,无论男性还是女性人群中冠心病组C等位基因携带者频率均显著高于正常对照组(男性:79.63％ vs.72.45％,P=0.02;女性:78.00％ vs.51.50％,P＜0.01),C等位基因携带者冠心病患病风险明显高于TT型(男性:OR=1.48,95％CI:1.06～2.09;女性:OR=3.34,95％CI∶1.90～5.86).(2)与无支架内再狭窄组相比,支架内再狭窄组C等位基因频率及C等位基因携带者分布频率均显著升高(C等位基因频率:72.39％ vs.54.84％,P＜0.01;CC+TC型:89.55％ vs.77.85％,P=0.027).与TT纯合子相比,C等位基因携带者支架内再狭窄患病风险升高2.44倍(95％ CI∶1.08～5.50).性别亚组分析表明,男性人群中支架内再狭窄组C等位基因携带者频率高于无支架内再狭窄组(92.86％ vs.77.66％,P=0.008),C等位基因携带者发生支架内再狭窄的风险是TT型的3.74倍(95％ CI∶1.32～10.64),而在女性人群中两组间(CC+TC)基因型分布频率无统计学意义(P=0.655).结论 CX37 C等位基因不仅与冠心病的发生发展有关联,而且与男性PCI术后支架内再狭窄的发生发展相关.     

Association of RANTES -403 G/A, -28 C/G and In1.1 T/C polymorphism with HIV-1 transmission and progression among North Indians

The relationships between host immune factors and HIV-1 disease progression are still in dispute. The RANTES SNPs exhibit distinct ethnic distribution and are associated with different effects on the course of HIV infection. Therefore, impact of RANTES gene polymorphism on HIV-1 transmission and progression needs to be evaluated. The RANTES genotypes were identified by PCR-RFLP method and confirmed by sequencing in HIV-1 seronegative (HSN; n=315), HIV-1 exposed seronegative (HES; n=47) and HIV-1 seropositive (HSP; n=196) patients classified into different clinical stages (i.e. Stages I, II, III). Fisher exact test was used for statistical analysis and Arlequin software for haplotype analysis. RANTES allele -403G, -28C and In1.1 T were the predominant allele in the subject studied. HSP group have higher frequency of RANTES In1.1 T allele compared with HSN (91.32% vs. 86.19%; P=0.013) and HES (91.32% vs. 78.72%; P=0.001). Higher frequency of RANTES In1.1 C allele in Stage III was observed, compared with Stage I (14.28% vs. 6.39%) and was significantly associated with high risk (P=0.047, OR=2.439, C.I.=1.061-5.609). Haplotype II (ACT) was significantly higher in HSP compared with HSN (9.69% vs. 1.58%) and associated with high risk (P<0.001, OR=6.655, C.I.=2.443-18.132). There were no significant differences in RANTES -403 A/G and -28 C/G genotype and allele distribution in all the groups compared. Our results implicate that RANTES In1.1 T allele and haplotype II (ACT) may be a risk factor for HIV-1 transmission while RANTES In1.1 C allele may be risk factor for disease progression among North Indians.     

纤维蛋白原β基因-148C/T多态性与脑梗死的关系

目的探讨纤维蛋白原（fibrinogen，Fg）β基因启动子区-148C／T多态性、血浆Fg水平与急性动脉粥样硬化性脑梗死的关系。方法用多聚酶链反应．限制性片段长度多态性方法对151例脑梗死患者和101名健康对照进行Fgβ-148C／T基因多态性分析，并应用凝血酶原时间衍生法检测血浆Fg水平。结果脑梗死组血浆Fg水平明显高于对照组（P〈0．01）；T等位基因携带者较CC基因型者血浆Fg水平明显增高（P〈0．01）；按性别分组后差异仍有统计学意义；按年龄段分组后，病例组各组T等位基因携带者较CC基因型者血浆Fg水平增高（P〈0．05）。中年梗死组较中年对照组T等位基因频率的差异有统计学意义（P〈0．05）。结论Fgβ-148C／T基因多态性影响血浆Fg水平，T等位基因可能独立或通过与其它血栓危险因素或环境因素协同作用增高血浆Fg水平，成为脑动脉血栓形成的危险因素。     

亲代MTHFR基因677C/T多态性与子代非综合征性唇腭裂的相关性

目的 探讨山东地区亲代亚甲基四氢叶酸还原酶( methylenetetrahydrofolate reductase,MTHFR)基因677C/T多态性与子代发生非综合征性唇腭裂(nonsyndromic cleft lip with or without cleft palate,NSCL/P)的关联.方法 应用聚合酶链反应-限制性片段长度多态性分析技术(polymerase chain reaction-restriction fragment length polymorphism,PCR-RFLP)对2006年8月至2008年8月在齐鲁医院治疗的89对NSCL/P患者亲代和64对健康查体儿童亲代的MTHFR基因677C/T多态性进行检测.结果 患者母亲与正常儿童母亲的T等位基因频率分别为65.73％和46.09％,C等位基因频率分别为34.27％和53.91％,其构成比差异有统计学意义(x2=13.663,P＜0.01);携带T等位基因的母亲子代患NSCL/P的风险为未携带T等位基因的母亲子代的2.243倍(95％CI:1.408～3.572).患者的父亲与正常儿童父亲的T等位基因频率分别为62.92％和55.47％ ;C等位基因频率分别为37.08％和44.53％,其构成比差异无统计学意义(x2 =2.222,P＞0.05);病例组和对照组后代可能为纯合突变胎儿的机率分别为43％和29％(P＞0.05).结论 山东地区母亲的MTHFR基因677C/T突变对后代NSCL/P的发生有重要的影响;父亲的MTHFR基因677C/T突变则可能不是子代患NSCL/P的风险因素.     

ERK5基因-322G/T多态性与散发性结直肠癌易感性的关系

目的: 探讨有丝分裂原活化蛋白激酶(MAPK)信号通路 ERK5 基因-322G/T(rs3866958)单核苷酸多态性与中国华南地区散发性结直肠癌(CRC)易感性的关系。方法: 采用Taqman-MGB荧光探针法检测华南地区835例肠癌和908例正常对照的 ERK5 基因-322G/T单个核苷酸的多态性。结果: ERK5 基因单核苷酸多态性位点-322G/T等位基因在结直肠癌患者和健康对照人群中分布差异无统计学意义(P>0.05),但在BMI≥24 kg/m²的肥胖人群中-322G/T的分布差异显著,与GG基因型相比,GT、TT基因型携带者的CRC发病风险下降42.4%(OR=0.576, 95%CI 0.413-0.804,P<0.01)。结论: ERK5 基因-322G/T单核苷酸多态性与结直肠癌发病无明显相关性,但可显著降低肥胖患者发病风险;-322T基因型是中国南方人群散发性结直肠癌肥胖患者的独立保护因素。     

醛固酮合成酶基因启动子-344T/C多态性与青海省汉族孕妇子痫前期的相关性

目的 探讨青海省汉族孕妇子痫前期(PE)与醛固酮合成酶基因(CYP11B2)启动子区单核苷酸多态性的关系.方法 选择青海省PE患者149例,正常妊娠对照组155例,应用聚合酶链反应-限制性内切酶片段长度多态性(PCR-RFLP)方法,分析PE组和对照组CYP11B2-344T/C多态性分型并测序验证.结果 PE组基因型...     

survivin基因启动子区-31C/G多态性与散发性结直肠癌遗传易感性的关系

目的： 探讨生存素survivin基因启动子区-31C/G单核苷酸多态性与中国华南地区散发性结直肠癌（CRC）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性法（PCR-RFLP）检测华南地区711例健康人和702例CRC的survivin基因-31C/G位点单核苷酸多态性。结果: 结直肠癌患者CC基因型的频率明显高于对照人群（36.5% vs 26.2 %,2=17.89,P<0.01）,与CC基因型相比,CG、GG基因型和等位基因G携带者的CRC发病风险分别显著下降至0.61倍（95%CI=0.46-0.80,P<0.01）、0.52倍（95%CI=0.38-0.71,P<0.01）和0.58倍（95%CI=0.45-0.74,P<0.01）。结论: survivin基因-31C/G多态与CRC发病风险有关,-31G变异基因型是中国南方人群散发性结直肠癌独立保护因素。     

Association between interleukin-18 gene polymorphism 105A/C and asthma

BACKGROUND: IL-18 has been shown to exert anti-allergic or allergy-promoting activities, but the existence of genetic polymorphisms in the coding regions of IL-18 gene has not been demonstrated. OBJECTIVE: The aim of this study was to investigate whether polymorphism is present in the coding regions of the IL-18 gene and, if so, to further analyse the association between polymorphism and asthma in a case-control study. METHODS: We screened the coding regions of the IL-18 gene for polymorphisms by using PCRsingle-stranded conformation polymorphism and direct sequencing of PCR products, followed by analysis of the association between polymorphism and asthma. RESULTS: We identified one polymorphism (105A/C) in the coding regions. The frequency of the 105A allele was significantly higher in asthmatic patients than in controls (P<0.01; odds ratio (OR)=1.83 (1.37-2.26)). Significant linkage disequilibrium was observed between the 105A/C and -137G/C polymorphisms in the 5' flanking region of the IL-18 gene (D=0.58, P<0.0001). However, in asthmatic patients the 105A allele was not associated with either total serum IgE or IL-18 levels. CONCLUSION: The 105A/C polymorphism of the IL-18 gene may be associated with the pathogenesis of asthma.     

Association between interleukin-10 -1082A/G, -819C/T and -592C/A polymorphisms with deep venous thrombosis

Background

Deep venous thrombosis (DVT) and inflammation are two closely related entities. The objective of this study was to evaluate a possible association between interleukin-10 (IL-10) -1082A/G, -819C/T and -592C/A polymorphisms with DVT.

Methods

A case-control study was carried out in 660 patients with DVT and 660 age- and gender-matched healthy controls. Polymerase chain reaction restriction fragment length polymorphism (PCR–RFLP) assay was applied to identify the polymorphisms mentioned.

Results

Patients with DVT had a significantly lower frequency of IL-10 -1082GG genotype [odds ratio (OR) = 0.59, 95% confidence interval (CI) = 0.39, 0.89; P = 0.01] than healthy controls. When stratifying by family history of DVT, it was found that patients with positive family history of DVT had a significantly lower frequency of IL-10 -1082GG genotype (OR = 0.13, 95% CI = 0.02, 0.95; P = 0.04). When stratifying by smoking status, presence of varicose veins, type 2 diabetes mellitus and any hormone administration before, no significant differences were found in any groups.

Conclusions

This study provides evidence that IL-10 -1082A/G polymorphism associated with risk of DVT. However, no association of the IL-10 -592C/A or -819C/T polymorphism with DVT risk was found. Additional well-designed large studies were required for the validation of our results.     

Association between ADAM33 T1 polymorphism and susceptibility to asthma in Asians

Objective

The aim of this study was to determine whether the ADAM33 (a disintegrin and metalloproteinase domain 33) T1 (rs2280091), T2 (rs2280090), and ST+7 (rs574174) polymorphisms confer susceptibility to asthma.

Methods

A meta-analysis stratified by ethnicity and age was conducted on associations between the ADAM33 T1, T2, and ST+7 polymorphisms and asthma.

Results

Eleven studies, which included 4,124 patients and 7,094 controls, were available for the meta-analysis. Meta-analysis revealed an association between asthma and the ADAM33 T1 GG genotype [odds ratio (OR)?=?2.257, 95?% confidence interval (CI)?=?1.577–3.228, p?=?8.42?×?10^?7]. Stratification by ethnicity indicated an association between this genotype and asthma in Asians (OR?=?2.683, 95?% CI?=?1.799–4.001, p?=?1.31?×?10^?7), and stratification by age indicated an association between it and asthma in adults (OR?=?1.895, 95?% CI?=?1.005–3.573, p?=?0.048). However, no association was found between asthma and the ADAM33 T2 and ST+7 polymorphisms.

Conclusions

This meta-analysis demonstrates that the ADAM33 T1 polymorphism confers susceptibility to asthma in Asians, but no association was found between the ADAM33 T2 and ST+7 polymorphisms and asthma susceptibility.     

白细胞介素1B-511多态性与侵袭性牙周炎的关系

目的研究中国人群中IL-1B-511位点单核苷酸多态性(single nucleotide polymorphism,SNP)与侵袭性牙周炎(aggressive periodontitis,AgP)之间的关系.方法提取122名AgP患者和95名健康对照者外周静脉血基因组DNA,应用聚合酶链反应-限制性片段长度多态性的方法,分析IL-1B-511位点SNP与AgP的关联性.结果男性AgP组杂合基因型的频率较男性健康对照组升高并有统计学意义(P=0.048);A2 基因型/等位基因A2与吸烟联合作用显著增加了AgP的易感性(基因型:P=0.022;等位基因:P=0.006).结论IL-1B-511位点的SNP可能与中国人群中男性个体的AgP易感性有关;该位点的SNP与吸烟可能对AgP的易感性具有联合效应.