TLR4基因多态性与感染性ARDS易感性的相关性研究

目的研究Toll样受体4(TLR4)基因Asp299Gly、Thr399Ile多态性与感染性急性呼吸窘迫综合征(ARDS)的关系。方法采用多聚酶链反应-限制性片段长度多态性(PCR-RFLP)方法,对40例感染性ARDS患者和50名健康人进行TLR4等位基因Asp299Gly和Thr399Ile的基因型检测。结果在感染性ARDS患者和健康体检者中,TLR4受体基因Asp299Gly、Thr399Ile两位点的基因型之间差异无统计学意义(χ2=0.043,P=0.635;χ2=0.071,P=0.583)。结论感染性ARDS患者的TLR4基因Asp299Gly和Thr399Ile多态性与感染性ARDS发病无显著相关性。     

TLR3和TLR4基因多态性与EV71感染手足口病严重性及易感性的关系研究

手足口病(Hand-foot-and-mouth disease,HFMD)是5岁以下婴幼儿常见的病毒性肠道传染病,该病主要由人肠道病毒71型(Enterovirus 71,EV71)型及柯萨奇A组16型(Coxsackievirus A16,CV-A16)引起,但关于TLR3、TLR4基因多态性与EV71感染手足口病的报道较少。为探讨EV71感染手足口病患儿TLR3和TLR4基因多态性与EV71感染手足口病严重性及易感性的关系,本研究选择2016年8月至2017年8月就诊于安徽医科大学第一附属医院的EV71感染手足口病患儿166例,其中重症组76例,轻症组90例,并选择同期来院体检的健康者120例作为对照组。收集患者入院时的年龄、性别、发热天数等基线资料,采集血液检测白细胞计数(White blood cell count,WBC)、丙氨酸转氨酶(Alanine aminotransferase,ALT)、谷草转氨酶(Glutamate transaminase,AST)、酶联免疫吸附试验(Enzyme-linked immunosorbent assay,ELISA)检测血清C反应蛋白(C reactive protein,CRP)、干扰素-γ(Interferon-γ,IFN-γ)水平;分离外周血单个核细胞提取DNA,琼脂糖凝胶电泳检测DNA情况;聚合酶链反应(Polymerase chain reaction,PCR)扩增TLR3c.1377C/T和TLR4-896A/G,限制性内切酶Tap I(TthHB8 I)、Nco I分别酶切TLR3、TLR4 PCR扩增产物,凝胶成像系统记录实验结果,对扩增产物进行测序,分析其基因多态性结果。结果显示,对照组与EV71感染组TLR3c.1377C/T位点的基因型分布与C、T等位基因频率均无显著统计学意义(P0.05);EV71感染组中重症组TT基因型较轻症组显著升高(P0.05);重症组T等位基因频率显著高于轻症组(P0.05),C等位基因频率显著低于轻症组(P0.05);EV71感染组中,TLR3c.1377C/T位点不同基因型患儿在年龄、性别及ALT、AST、CKMB水平上无显著差异(P0.05);TLR3c.1377C/T位点TT型患儿的发热时间及WBC、CRP水平显著高于CT和CC型,CT型患儿的发热时间及WBC、CRP水平显著高于CC型(P0.05);CC型患儿的IFN-γ水平显著高于CT和TT型(P0.05);TLR4-896A/G基因电泳条带为140bp的特异性扩增产物,为野生型Asp/Asp基因型,对照组和EV71感染组均未出现A→G的突变。本研究得出结论,TLR3c.1377C/T位点有CC、TT、CT三个基因型,且携带T等位基因EV71感染手足口病患儿进展为重症的风险较高;TLR4-896A/G基因无突变,与EV71感染手足口病患儿疾病严重性和易感性无关。     

外周血TLR2和TLR9在小儿复发性单纯疱疹中的作用

目的:研究外周血Toll受体2(TLR2)和Toll受体9(TLR9)在小儿复发性单纯疱疹(RHS)中的作用。方法:选择从2014年1月至2016年12月在我院就诊的RHS患儿46例纳入本次研究,将其记为观察组。另选同期在我院进行健康体检的儿童45例作为对照组。对比两组外周血TLR2及TLR9水平,白细胞介素-2(IL-2)、白细胞介素-4(IL-4)及C反应蛋白(CRP)水平,采用Spearman相关性分析患儿外周血TLR2及TLR9水平与其炎症指标的相关性。结果:观察组外周血TLR2、TLR9和TLR2及TLR9双表达的水平均明显高于对照组(P0.05)。观察组的IL-2水平较对照组降低(P0.05),IL-4及CRP水平较对照组升高(P0.05)。Spearman相关性分析显示,患儿外周血TLR2及TLR9水平与其IL-2呈负相关(P0.05),与IL-4和CRP呈正相关(P0.05)。结论:TLR2和TLR9在RHS患儿外周血中均具有较高表达,且与机体炎症因子IL-2、IL-4及CRP间具有紧密联系,值得临床重视。     

一例以多发性骨破坏为显著特征的老年戈谢病的诊疗和基因检测分析

戈谢病(Gaucher’s disease)是一种罕见的常染色体隐性遗传病，由于葡萄糖脑苷脂酶(glucocerebrosidase,GBA)基因突变导致溶酶体中GBA活性降低或缺乏，造成其底物葡萄糖脑苷脂在溶酶体中贮积，产生肝、脾、肾、骨、造血系统甚至神经系统受累的临床表现。本文报道1例以多发性骨破坏为显著特征的老年患者，伴有幼年脾切除及“骨髓炎”病史，呈现肝脏显著增大、贫血、血小板减少及骨量减少等症状。临床检测显示，患者外周血GBA活性降低、葡糖鞘氨醇水平以及壳三糖酶活性显著升高；基因检测结果表明，患者GBA基因发生纯合错义突变NM＿001005741.2 c.770A>G(p.Asp257Gly)。经过6个月的酶替代治疗，患者血小板恢复正常、贫血改善、肝脏体积有所缩小。进一步检测发现患者母亲、长兄、次兄均存在该位点的杂合突变，符合孟德尔遗传规律。虽然患者Asp257Gly变异在已知的GBA基因变异库中未被报道，但无论是临床表现还是酶学及生物标记物特征，以及酶替代治疗的效果，均支持戈谢病的诊断，推断患者Asp257Gly纯合变异为临床致病性变异。本病例发现的新突变位点丰富了G...     

大肠杆菌glgC基因的定点突变及功能分析

摘要: 利用PCR从Escherichia coli JM109基因组中扩增到全长为1 296 bp的glgC基因编码区, 通过PCR重组方法进行点突变, 获得氨基酸突变的3个突变体, 分别是Pro295Ser(Val121Ala, Met151Ile和Val334Asp)、Gly336 Asp单点突变和Pro295Ser/Gly336Asp(Lys109Arg), 其基因分别命名为295⁺³、336和295/ 336⁺¹。将突变和未突变的基因分别克隆到pET32-a, 构建重组质粒pET-glgC、pET-295⁺³、pET-336和pET-295/ 336+1, 在文中分别简称为a、b、c和d。转化大肠杆菌BL21(DE3), 在1 mmol/L IPTG 诱导下表达。SDS- PAGE 电泳分析显示, 在约67 kDa 处有1条明显与预期大小一致的蛋白质, 表明目的基因已得到融合表达。上述转化子的碘染和糖原含量测定结果, 第336位的Gly变成Asp后, 宿主菌的糖原含量提高; Pro295Ser/Gly336Asp(Lys109Arg)的突变导致宿主菌的糖原含量与Gly336Asp突变体相近, 表明在336突变基因的基础上增加Pro295Ser的突变没有进一步加大宿主菌中AGPase酶的反馈抑制效应的降低。已有的结果显示, Pro295Ser可以降低AGPase酶的反馈抑制效应活性, 而实验中295⁺³突变基因转入宿主菌后细胞糖原含量明显降低, 推测这个结果可能是295⁺³中的Val334Asp的突变造成, 而334位的氨基酸可能是AGPase功能域中的一个重要位点。     

非小细胞肺癌患者K-ras基因突变与预后的相关性分析

目的:探讨非小细胞肺癌(NSCLC)患者K-ras基因突变与预后的相关性。方法:回顾分析2006年3月~2008年7月江西省肿瘤医院收治的92例NSCLC患者的临床资料,所有患者均采用蝎形探针扩增阻遏突变系统(ARMS)法行K-ras基因突变检测。结果:92例NSCLC患者中,11例K-ras基因突变阳性,阳性率为11.96%,包括Gly12Cys(GGTTGT)突变3例、Gly12Val(GGTGTT)突变2例、Gly12Ala(GGTGCT)突变2例、Gly12Arg(GGTCGT)突变2例、Gly12Cys(GGTTGT)突变与Gly12Val(GGTGTT)突变并存1例、Gly12Cys(GGTTGT)突变与Gly12Ala(GGTGCT)突变并存1例;K-ras基因突变阳性组与阴性组之间的患者性别、年龄、病理类型、吸烟史相比,差异无统计学意义(P0.05);K-ras基因突变阳性组Ⅲa~Ⅳ期患者中位生存期显著低于K-ras基因突变阴性组Ⅲa~Ⅳ期患者,差异有统计学意义(P0.05)。结论:NSCLC患者K-ras基因突变阳性率较低,但它可以对NSCLC患者预后产生负性影响。     

TLR4基因启动子区多态性及其对蛋白表达的影响

目的:检测中国人群Toll样受体4(Toll-like receptor 4,TLR4)基因5′调控区的单核苷酸多态性(single nucleotidepolymorphisms,SNPs),探讨其与TLR4蛋白表达的关系.方法:采用聚合酶链反应-限制性片段长度多态性法(PCR-RFLP)对正常汉族人群样本TLR4启动子区-2242、-1892和-1837这3个可能有意义的SNP位点进行基因分型,以确定中国人群中TLR4基因启动子区SNP基因型和发生频率.取其中89例全血标本用全血培养模型检测内毒素刺激前后TLR4蛋白的表达变化,进一步探讨TLR4启动子区单核苷酸多态性对其蛋白表达的影响.结果:TLR4启动子区-2242、-1892和-1837这3个可能有意义的SNP住点等位基因频率分别是43.27%、27.70%和42.75%.TLR4蛋白表达检测结果表明内毒素刺激后-2242位点TC与CC基因型TLR4蛋白的表达显著高于TT基因型(P<0.05),其它位点则没有影响.结论:中国汉族人群中TLR4基因启动子区-2242位点可能是脓毒症关联分析重要的遗传标记.     

肌萎缩侧索硬化患者SOD1基因突变检测及突变与临床表型的关系

应用PCR技术结合DNA直接测序方法对8例临床确诊为家族性肌萎缩侧索硬化(Familiar amyotrophic lateral sclerosis,FALS)家系的先证者进行铜锌超氧化物歧化酶基因(SOD1)的突变筛查,在3例先证者中检出2种SOD1基因突变,其中,2例携带了位于4号外显子的错义突变Cys111Tyr(c.332G>A),另1例携带了位于5号外显子的错义突变Gly147Asp(c.440G>A),这2种突变在中国ALS患者中属首次报道。该结果扩大了中国FALS患者的SOD1基因突变谱,对研究中国FALS患者SOD1基因突变特点和分布规律有一定帮助。分析携带这2个突变患者的临床特点,提示Cys111Tyr突变导致的临床表型相对温和,而Gly147Asp突变可导致病情进展较快。该结果有待在更多的病例中进行证实。     

ABCA1基因多态性R219K与帕金森症和阿尔兹海默症发病率的相关性研究

目的:探讨与研究三磷酸腺苷结合盒转运体A1 (Adenosine triphosphate (ATP)-binding cassette transporter A1)基因多态性R219K与帕金森症(Parkinson disease,PD)和阿尔兹海默症(Alzheimer disease,AD)发病率的相关性。方法:选择2016年2月到2019年8月在本院门诊与住院的帕金森症患者42例作为PD组,同期选择本院门诊与住院的阿尔兹海默症患者42例作为AD组,同期选择本院门诊健康体检者84例作为对照组。调查入选者的一般资料,检测三组血液样本的ABCA1基因多态性R219K情况并进行相关性分析。结果:AD组低密度脂蛋白(low-density lipoprotein,LDL-C)、总胆固醇(total cholesterol,TC)、甘油三酯(triglyceride,TG)与尿酸(Uric acid,UA)均低于对照组,而高密度脂蛋白(high-density lipoprotein,HDL-C)、同型半胱氨酸(homocysteine,Hcy)值高于对照组(P0.05);AD组TC均低于PD组,而HDL高于PD组。PD患者HDL-C均低于对照组,而LDL、TC和TG与对照组无差异(P0.05),三组空腹血糖(Fasting blood glucose,FBG)值对比差异无统计学意义(P0.05)。PD组与AD组的ABCA1 R219K GA基因型、A等位基因频率都显著高于对照组(P0.05),PD组与AD组对比差异无统计学意义(P0.05)。在168例入选者中,直线相关分析显示ABCA1 R219K GA基因型与A等位基因与帕金森症或阿尔兹海默症发生有显著相关性(P0.05)。结论:ABCA1基因多态性R219K在帕金森症和阿尔兹海默症患者中比较常见,ABCA1 R219K GA基因型与A等位基因可诱发帕金森症和阿尔兹海默症的发生。     

载脂蛋白E与阿尔茨海默病的关系

阿尔茨海默病(Alzheimer disease,AD)是最常见的一种老年性痴呆症,临床上以进行性记忆丧失和认知功能障碍为特征。流行病学资料表明,载脂蛋白E(apolipoprotein E,ApoE)的基因多态性与AD密切相关。ApoE不但影响了AD的发生年龄与危险性,还与AD特征性病理改变神经原纤维缠结(neurofibrillary tangle,NFT)和老年斑(senile plaque,SP)共定位。研究发现,ApoE可促进β-淀粉样肽(β—amyloid peptide,Aβ)的沉积和SP的形成,C末端切除的ApoE片段则促使Tau蛋白的过度磷酸化及NFT的形成,并进一步引起神经变性和行为缺陷。同时,ApoE还与炎症因子的表达相关。上述证据均提示了ApoE及其基因多态性在AD发病机制中的重要作用。     

TLR4 and TLR9 polymorphism: Probable role in susceptibility among the population of Bihar for Indian visceral leishmaniasis

Genetic variations in the host TLRs genes play an important role in susceptibility and/or resistance to visceral leishmaniasis by altering the host-pathogen interaction. In this study, we investigated the association between polymorphisms of TLR4 (Asp299Gly, Thr399Ile) and TLR-9 (T-1237C), with susceptibility to visceral leishmaniasis. A bi-directional PCR amplification of specific alleles technique was used to characterize the distribution of TLR4 (Asp299Gly and Thr399Ile) and TLR9 (T-1237C) polymorphisms. A total of 60 samples were randomly selected from confirmed visceral leishmaniasis patients and 24 endemic healthy volunteers. The samples were genotyped and allele frequencies were determined. We observed that TLR4 Asp299Gly and Thr399Ile genotypes were more frequent in visceral leishmaniasis patients (10% and 15% respectively) compared to controls (4.2% and 8.3% respectively). However, the differences were not significant in TLR4 Asp299Gly and Thr399Ile alleles and genotypes. In the case of TLR9, we observed the frequency of T1237C genotype was higher in visceral leishmaniasis patients (43.3%) than in healthy controls (33.3%). Statistically significant differences were observed in TLR9 T1237C alleles and genotypes. We concluded that TLR9 T1237C, but not TLR4, gene polymorphisms can be regarded as contributors to visceral leishmaniasis susceptibility among the Indian population of Bihar state.     

Toll-like receptor 4 Asp299Gly/Thr399Ile polymorphisms are a risk factor for Candida bloodstream infection

Toll-like receptor (TLR)-4 is an important pattern recognition receptor for Candida albicans, playing a role in innate host defense. We investigated whether there is an association between the TLR4 Asp299Gly or TLR4 Thr399Ile polymorphism, and the occurrence of Candida bloodstream infection. We performed a case-control study, involving 43 patients with a Candida bloodstream infection and 166 healthy individuals. TLR4 Asp299Gly and Thr399Ile polymorphisms were assessed, as well as cytokine production after stimulation of peripheral blood mononuclear cells (PBMC) with Candida albicans. We observed that the prevalence of TLR4 Asp299Gly polymorphism was found to be higher in patients with Candida bloodstream infection than in controls (26% versus 10%; OR 3.0; 95%CI 1.3-6.9). All patients bearing the Asp299Gly polymorphism were also positive for the Thr399Ile allele, a linkage well described in literature. IL-10 production was higher in C. albicans-stimulated PBMC from volunteers bearing the TLR4 Asp299Gly polymorphism, and a similar tendency was observed in TLR4 Asp299Gly heterozygous patients who had recovered from candidemia. These findings show that the TLR4 Asp299Gly/Thr399Ile polymorphisms are associated with an increased susceptibility to Candida bloodstream infections, and an increased production of IL-10 is probably involved in this effect.     

Functional consequences of the Asp299Gly Toll-like receptor-4 polymorphism

Toll-like receptor-4 (TLR4) is a pattern-recognition receptor not only for exogenous ligands such as lipopolysaccharide (LPS) of Gram-negative bacteria, but also for endogenous ligands such as fibronectin, heat shock proteins and hyaluronan oligosaccharides. The Asp299Gly allele of the TLR4 gene has been associated with increased risk for severe infections, but reduced progression of atherosclerosis. We have investigated the consequences of the presence of Asp299Gly polymorphism after stimulation of mononuclear cells with lipopolysaccharide (LPS), the non-LPS TLR4 microbial stimuli Aspergillus fumigatus and Cryptococcus neoformans, and the endogenous TLR4 ligand heat shock protein 60. No differences in either production of the proinflammatory cytokine TNF or the antiinflammatory cytokine interleukin-10 were observed between volunteers with the wild-type allele, volunteers heterozygous for the Asp299Gly allele and one volunteer homozygous for the TLR4 variant. In conclusion, the presence of the Asp299Gly TLR4 polymorphism does not result in defective pro and antiinflammatory cytokine production after stimulation with either exogenous (LPS and non-LPS) or endogenous TLR4 ligands, and alternative explanations are likely to be responsible for the epidemiological data showing associations with inflammatory conditions. In addition, this is the first study to demonstrate that even homozygosity for the Asp299Gly mutation does not confer hyporesponsiveness to stimulation with TLR4 stimuli.     

The Toll-Like Receptor 4 Polymorphism Asp299Gly but Not Thr399Ile Influences TLR4 Signaling and Function

The common, co-segregating Toll-like receptor 4 (TLR4) non-synonymous single nucleotide polymorphisms (SNPs), Asp299Gly and Thr399Ile, are associated with hyporesponsiveness to inhaled lipopolysaccharide (LPS) and increased susceptibility to Gram negative pathogens in humans. The purpose of this study was to identify the relative contributions of the Asp299Gly and the Thr399Ile variants in inhibiting the function of TLR4. 293/hMD2-CD14 cell line was transfected with lentiviral constructs containing human wild type (WT) TLR4-EGFP or TLR4-EGFP with Asp299Gly, Thr399Ile or Asp299Gly/Thr399Ile complementary DNA (cDNA). Multiple stable cell lines were established for each construct: three for WT TLR4, Asp299Gly, and Thr399Ile, and only two for Asp299Gly/Thr399Ile mutants and EGFP control. We did not observe a significant effect of polymorphisms on cell surface and intracellular TLR4 expression nor were there any significant differences in TLR4 and EGFP protein levels assessed by Western blotting and confocal microscopy among the multiple cell lines of each of the constructs. All cell lines had a dose-dependent responsiveness to LPS stimulation. However, compared to the WT TLR4, cells expressing TLR4 with Asp299Gly but not Thr399Ile polymorphism produced significantly less (P<0.05) IL-8 following LPS stimulation. Similarly, cells expressing TLR4 Asp299Gly but not Thr399Ile allele had significantly lower percentage of phosphorylated and total NF-κB P65 following LPS stimulation. While we could not do statistics on the Asp299Gly/Thr399Ile group, we observed a reduced responsiveness to LPS compared to WT TLR4. Taken together, we observed that the TLR4 Asp299Gly variant, but not the Thr399Ile variant, is responsible for impaired responsiveness of TLR4 to LPS and corresponding activation of NF-κB.     

Toll-like receptor polymorphisms and vasculitis susceptibility: meta-analysis and systematic review

The aim of this study was to determine whether toll-like receptor (TLR) polymorphisms confers susceptibility to vasculitis. A literature search was conducted using the PubMed and Embase. A meta-analysis on the associations between the TLR4 Asp299Gly polymorphisms and vasculitis was carried out using allele contrast, dominant, and codominant models and a systematic review of other TLR polymorphisms. Fourteen studies involving 2,064 patients and 2,481 controls were included in this systematic review, which comprised nine on Behcet’s disease (BD), three on giant cell arteritis (GCA), and one on Henoch–Schenlein purpura (HSP). Meta-analysis of six studies showed a significant association between the Gly/Gly+Gly/Asp genotype of the TLR4 Asp299Gly polymorphism and vasculitis and GCA (Odds ratio [OR] = 1.368, 95 % confidence interval [CI] = 1.300–1.815, p = 0.030; OR = 1.523, 95 % CI = 1.099–2.112, p = 0.012). Under a random effects model, the adjusted ORs calculated using the trim and fill technique revealed an association between the Gly/Gly+Gly/Asp genotype of the TLR4 Asp299Gly polymorphism and vasculitis (OR = 1.544, 95 % CI = 1.091–2.185, p < 0.05). Stratification by vasculitis type using the codominant model showed the trend for the association with GCA (OR = 1.569, 95 % CI = 0.970–2.538, p = 0.066). There were three studies on the TLR2 Arg753Gln polymorphism and two on the TLR4 Thr399Ile polymorphism; no association with vasculitis was evident. Among the TLR2, TLR7, and TLR9 polymorphisms included in this review, one Asian study revealed a significant association between the TLR7 rs5743733 and rs3853839 with BD (p = 0.002, 0.036) and one Asian study showed an association of TLR9 rs352140 with BD (p = 0.009). This meta-analysis demonstrates that the TLR4 Asp299Gly polymorphism may confer susceptibility to GCA. The review of published data suggests that other TLR polymorphisms such as TLR7 and TLR9 may play a role in vasculitis.     

Individual LPS responsiveness depends on the variation of toll-like receptor (TLR) expression level

An individual's immune response is critical for host protection from many different pathogens, and the responsiveness can be assessed by the amount of cytokine production upon stimulating bacterial components such as lipopolysaccharide (LPS). The difference between individuals in their peripheral blood mononuclear cells (PBMC) responsiveness to LPS, a Gram-negative endotoxin, was investigated from 27 healthy individuals. We observed a large variation in IFNgamma production among different individuals. The PBMC of the consistently three highest and three lowest IFNgamma producers were investigated. Since previous studies described that a single point mutation in the coding region of TLR2 and TLR4 is linked to the individual responsiveness to pathogenic bacterial infections, we first examined the known point mutations in the coding region of TLR2Pro681His, TLR4Pro714His located in the cytoplasmic regions of the Toll-like domain as well as TLR4Asp299Gly located in the extracellular region. None of these mutations were associated with an individual's responsiveness to LPS, despite the presence of TLR4Asp299Gly mutation. Further investigation revealed that the variation of PBMC responsiveness to LPS among healthy individuals was due to constitutive expression levels of TLR4 and TLR2. This result is consistent with an aging-related low expression of Toll-like receptors in the mouse model of LPS responsiveness. The present study therefore suggests that the constitutive expression levels of TLR2 and TLR4 may contribute to the individual response to LPS.     

Toll-like receptor 4 polymorphisms predispose to cutaneous leishmaniasis

The clinical spectrum of cutaneous leishmaniasis (CL) is extremely variable. Studies in experimental leishmaniasis have revealed a role for TLR4 in control of infection. In the present study the associations between TLR4 mutations (Asp299Gly and Thr399Ile) with outcome of CL have been investigated. Genotyping for Asp299Gly and Thr399Ile was performed in patients with chronic (N?=?22) and acute (N?=?61) CL, asymptomatic (N?=?45) and healthy leishmanin skin test negative individuals (N?=?75). The results showed the frequency of the Asp299Gly genotype was increased in patients with chronic disease (OR 25.3, 95% CI 5.2-115.6, P?相似文献   

Relationship between the TLR2 and TLR4 gene polymorphisms with a predisposition to certain urogenital infections

The distribution of the TLR2 Arg753Gln, TLR4 Asp299Gly and TLR4 Thr399Ile polymorphisms among residents of Poltavsky region was studied. The relationship between these polymorphisms and the presence of diseases caused by urogenital infections was also studied. The population control group was a random sample of residents of Poltavsky region (n = 299); the group of patients with urogenital diseases consisted of 156 individuals. PCR and subsequent restriction analysis were used to enable the genotyping of the following TLR polymorphisms in these groups: Arg753Gln, Asp299Gly, and TLR4 Thr399Ile. We found a statistically significant correlation between the presence of allele A of the TLR2 gene (p = 0.0018) and allele G of the TLR4 gene (p = 0.085) and the presence of urogenital diseases.     

Relationship of TLR2 and TLR4 gene polymorphism with a penchant for individual urogenital infections

We investigated the population prevalence of polymorphisms of Arg753Gln TLR2gene, and Asp299Gly, Thr399Ile TLR4 genes among people living in the Poltava region, as well as data communication polymorphisms with the presence of diseases caused by urogenital infections. The group of population control was a random sample of residents of the Poltava region (n = 299). The group of patients with urogenital diseases included 156 people. Genotyping of these groups TLR2 Arg753Gln polymorphism and the gene TLR4 Asp299Gly, Thr399Ile was performed using PCR and subsequent restriction analysis. Statistically significant association of allele A ofgene TLR2 (p = 0.0018) and allele G of gene TLR4 (p = 0.085) with the presence of urogenital diseases was confirmed.     

TLR4 and TLR9 polymorphisms are not associated with either rheumatoid arthritis or systemic lupus erythematosus in Mexican patients

Toll-like receptor (TLR)-mediated signaling pathways induce a proinflammatory microenvironment to eradicate pathogens. However, in rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE), TLRs can promote chronic inflammation. It has been shown that some TLR4 and TLR9 single nucleotide polymorphisms (SNPs) are risk factors for RA and SLE, but these findings have not been replicated in all populations; thus, results are inconclusive. We evaluated the TLR4 Asp299Gly, Thr399Ile,???1892G/A SNPs, and the TLR9 Pro545Pro SNP to assess potential associations with RA and SLE in Mexican patients. This study included 474 patients with RA, 283 patients with SLE, and 424 healthy controls. We used a 5′ nuclease allelic discrimination assay to genotype individuals for the four TLR4 and TLR9 polymorphisms. We found that the genotype or allelic frequencies of the TLR4 Asp299Gly, Thr399Ile,???1892G/A, and TLR9 Pro545Pro polymorphisms were similar between patients and controls. We found no association under different genetic models. A haplotype analysis of TLR4 showed no association with either RA or SLE. We found no significant differences in the allelic or genotypic frequencies of TLR4 Asp299Gly, Thr399IIe,???1892G/A, or TLR9 Pro545Pro between patients and controls. These findings suggested that these variants are not risk factors for RA or SLE in Mexican patients.