Lack of association of Toll-like receptor 9 polymorphisms with susceptibility to systemic lupus erythematosus in an Asian population: a meta-analysis

The association of Toll-like receptor 9 (TLR9) gene polymorphisms with systemic lupus erythematosus (SLE) risk remains controversial and ambiguous. To more precisely estimate the relationship between TLR9 gene polymorphisms and the susceptibility to SLE, a meta-analysis was performed. A total of seven independent studies were involved in this analysis. Meta-analysis was performed for three TLR9 gene polymorphisms (rs187084, rs352139, and rs352140). We have compared allele or genotype frequencies of the polymorphisms in SLE patients and controls. When available studies were pooled into the meta-analysis, there was no evidence showing a significant association between rs187084 and SLE risk in an Asian population (for C vs. T: OR?=?0.81, P?=?0.117; for CC vs. TT: OR?=?0.71, P?=?0.158; for CT vs. TT: OR?=?0.86, P?=?0.085; for CC?+?CT vs. TT: OR?=?0.78, P?=?0.093; for CC vs. CT?+?TT: OR?=?0.81, P?=?0.285). Similar results were found between rs352139 and SLE. No significant association was detected in any genetic model in the Asian population either (for G vs. A: OR?=?1.11, P?=?0.095; for GG vs. AA: OR?=?1.32, P?=?0.238; for GA vs. AA: OR?=?1.17, P?=?0.084; for GG?+?GA vs. AA: OR?=?1.17, P?=?0.073; for GG vs. GA?+?AA: OR?=?1.17, P?=?0.404). We found no association between TLR9 gene rs352140 polymorphism and SLE in the Asian population (for A vs. G: OR?=?1.02, P?=?0.728). In conclusion, there is still not enough evidence to indicate an association between TLR9 gene rs187084, rs352139, and rs352140 polymorphisms and the development of SLE in the Asian population.     

Lack of association of Toll-like receptor 9 polymorphisms with susceptibility to systemic lupus erythematosus in an Asian population: a meta-analysis

Abstract

The association of Toll-like receptor 9 (TLR9) gene polymorphisms with systemic lupus erythematosus (SLE) risk remains controversial and ambiguous. To more precisely estimate the relationship between TLR9 gene polymorphisms and the susceptibility to SLE, a meta-analysis was performed. A total of seven independent studies were involved in this analysis. Meta-analysis was performed for three TLR9 gene polymorphisms (rs187084, rs352139, and rs352140). We have compared allele or genotype frequencies of the polymorphisms in SLE patients and controls. When available studies were pooled into the meta-analysis, there was no evidence showing a significant association between rs187084 and SLE risk in an Asian population (for C vs. T: OR = 0.81, P = 0.117; for CC vs. TT: OR = 0.71, P = 0.158; for CT vs. TT: OR = 0.86, P = 0.085; for CC + CT vs. TT: OR = 0.78, P = 0.093; for CC vs. CT + TT: OR = 0.81, P = 0.285). Similar results were found between rs352139 and SLE. No significant association was detected in any genetic model in the Asian population either (for G vs. A: OR = 1.11, P = 0.095; for GG vs. AA: OR = 1.32, P = 0.238; for GA vs. AA: OR = 1.17, P = 0.084; for GG + GA vs. AA: OR = 1.17, P = 0.073; for GG vs. GA + AA: OR = 1.17, P = 0.404). We found no association between TLR9 gene rs352140 polymorphism and SLE in the Asian population (for A vs. G: OR = 1.02, P = 0.728). In conclusion, there is still not enough evidence to indicate an association between TLR9 gene rs187084, rs352139, and rs352140 polymorphisms and the development of SLE in the Asian population.     

TLR7/8/9 polymorphisms and their associations in systemic lupus erythematosus patients from southern Brazil

Systemic lupus erythematosus (SLE) is a chronic inflammatory autoimmune disease and can affect several organs and systems. It is characterized by high production of autoantibodies against nuclear compounds. TLR7/8/9 are responsible for nucleic acid recognition and they trigger proinflammatory responses through activation of NK-kappaB and Type I IFN production, making a bridge between the innate and the adaptative immune systems. We analyzed the frequency of TLR7 rs179008, TLR8 rs3764880, TLR9 rs5743836 and rs352140 in 370 patients with SLE and 415 healthy controls from southern Brazil. All analyses were conducted with regard to gender and ethnicity. Genotypic and allelic frequencies were different for TLR7 rs179008 (0.253 vs. 0.163, p = 0.020 and p = 0.003, OR for T allele: 1.74 CI 95% 1.12-2.70) and TLR9 rs5743836 (0.174 vs. 0.112, p = 0.045 and p = 0.017, OR for C allele: 1.59, CI 95% 0.99-2.57) between European-derived female groups. A higher frequency was observed for the presence of Anti-SSa/Ro for TRL9 rs5743836 C allele carriers (0.228 vs 0.126, Bonferroni corrected p = 0.06). No statistical differences were found for TLR9 haplotypic analyses. We suggest that TLR7 rs179008 and TLR9 rs5743836 can be considered SLE susceptibility factors for women of European descent in our population.     

江苏汉族人群白细胞介素-23受体基因多态性与炎症性肠病及其表型的关系

目的 探讨江苏汉族人群中IL-23受体基因多态性与炎症性肠病及其表型的关系.方法 选取178例炎症性肠病患者[溃疡性结肠炎(UC) 135例,克罗恩病(CD)43例]和134例健康对照,检测IL-23受体基因的6个单核苷酸多态性位点(rs1 1805303、rs1343151、rs11465804、rs11209032、rs17375018、rs11465788)的基因多态性,分析其与UC、CD各临床表型的关联性.结果 rs 11805303的T等位基因频率在UC中为60.4％,高于对照组(50.4％),P=0.020.UC的基因-表型分析显示,rs17375018位点的基因多态性与结肠炎活动性指数(UCDAI)即UC的严重程度相关,携带等位基因G的患者倾向于发生轻度UC.CD的基因-表型分析显示,rs17375018位点的A等位基因频率在诊断年龄≤25岁的CD患者中明显高于诊断年龄＞25岁的患者(41.7％比22.0％,P=0.050,OR=2.532,95％ CI0.988～6.494);rs11805303位点的基因型与CD的诊断年龄、病变范围有关联性(P值分别为0.039和0.044);rs 17375018位点的A等位基因携带者发生肠外表现的几率较等位基因G携带者低(23.1％比46.7％,P=0.040,OR =2.917,95％ CI1.027～8.283).结论 在江苏汉族人群中,rs11805303是UC的易感基因位点,同时rs11805303、rs17375018位点的基因多态性与UC、CD的临床表型有关联性.     

Toll样受体(TLR)2、TLR4和TLR9在大鼠结肠炎模型结肠组织中的表达及其意义

Toll样受体（TLRs）家族可能在一系列免疫性疾病中发挥重要作用。目的：观察TLR2、TLR4和TLR9在大鼠结肠炎模型结肠组织中的表达，探讨三者在炎症性肠病（IBD）发病机制中的作用。方法：以三硝基苯磺酸（TNBS）＋乙醇灌肠制备大鼠结肠炎模型，观察和评估结肠黏膜的大体和组织学变化。分别以黄嘌呤氧化酶法和紫外分光光度法测定超氧化物歧化酶（SOD）和髓过氧化物酶（MPO）活性；以免疫组化方法检测TLR2、TLR4和TLR9的表达，以逆转录聚合酶链反应（RT-PCR）检测三者mRNA的表达。结果：造模后结肠组织中可见大量炎性细胞浸润，累及黏膜下层和固有层。与正常对照组相比，模型组结肠组织SOD活性显著降低（P〈0．01），MPO活性显著升高（P〈0．01）。正常对照组结肠黏膜下层和固有层炎性细胞胞膜和胞质仅有少量TLR2、TLR4表达，未见TLR9表达；模型组三者表达均显著增加（P〈0．01），此外还可见TLR2表达于肠上皮近肠腔侧胞膜，TLR4表达于肠上皮近肠腔侧胞膜和腺上皮近腺腔侧胞膜。模型组结肠组织可见TLR2、TLR4、TLR9 mRNA表达，而正常对照组未检出三者mRNA的表达。TLR2、TLR4、TLR9的表达与MPO活性呈正相关（P〈0．05），与SOD活性呈负相关（P〈0．01）。结论：大鼠结肠炎模型结肠组织中TLR2、TLR4和TLR9表达明显增加，可能与结肠的自身免疫损伤有关。     

TLR9 polymorphisms and systemic lupus erythematosus risk: an update meta-analysis study

It has been reported that the Toll-like receptor 9 (TLR9) gene polymorphisms may be associated with systemic lupus erythematosus (SLE) risk. However, some studies yielded conflicting results. Therefore, a comprehensive meta-analysis was performed to assess the precise association between TLR9 polymorphisms and SLE susceptibility. We performed a systematic search in PubMed, Embase (Ovid), China National Knowledge Internet, and Wanfang databases up to July 15, 2015. Odds ratio (OR) and 95 % confidence interval (CI) were used to pool the effect size. Statistical analyses were performed with STATA 11.0 software. In total, 21 studies from nineteen articles with 10,273 subjects were included in this meta-analysis. The overall results suggested that there was a statistically significant association between TLR9 rs187084 polymorphism and SLE risk observed in recessive model (TT vs. TC + CC: OR 1.17, 95 % CI 1.05–1.30, P = 0.005), codominant model (TT vs. CC: OR 1.22, 95 % CI 1.03–1.43, P = 0.019), and allele model (T vs. C: OR 1.15, 95 % CI 1.02–1.30, P = 0.020) in Asians. However, we found that there may be no significant association between the other three TLR9 polymorphisms and SLE risk in either Asians or non-Asians. In conclusion, the meta-analysis results suggested that TLR9 rs187084 polymorphism may increase the risk of SLE in Asians. However, no significant association between TLR9 SNPs (rs352139, rs352140, and rs5743836) and SLE risk was identified.     

Toll-Like Receptor Gene Polymorphisms and Susceptibility to Epstein–Barr Virus-Associated and -Negative Gastric Carcinoma in Northern China

Background/Aims:

Various polymorphisms in toll-like receptor (TLR) genes have been identified and associated with susceptibility to various malignancies, such as gastric carcinoma (GC), breast cancer, and prostate cancer. However, little is known about the polymorphisms of TLR genes and the susceptibility to GC in Northern China, especially to Epstein–Barr virus-associated GC (EBVaGC). We focused on the association with susceptibility to GC, especially to EBVaGC.

Patients and Methods:

Polymorphisms of the TLR2, 3, 4, and 9 genes were measured in 52 cases of EBVaGC and 157 cases of EBV-negative GC (EBVnGC). Ninety-four peripheral blood samples from healthy individuals were also examined.

Results:

For the TLR2 gene (196 to 174 del), there was no significant difference between the GC group and control group in genotype, but there was a significant difference in the del allele. As for the TLR3 gene (c. 1377C/T), there were significant differences between the GC group and the control group in both genotype and allelic frequency. No SNPs single nucleotide polymorphisms (SNPs) were found in the TLR4 gene at the sites Asp299Gly and Thr399Ile. As for TLR9 1486T/C (rs187084) and C2848T (rs352140), there was also no association between the GC group and control. In all of the indicators, there were no significant differences between EBVaGCs and EBVnGCs.

Conclusions:

The TLR3 gene (c. 1377C/T) polymorphisms and the del allele of the TLR2 gene (196 to 174) were both associated with susceptibility to GC in Shangdong Province of Northern China. There was no interaction between EBV and TLR gene polymorphisms in EBVaGC.     

The investigation of toll-like receptor 3, 9 and 10 gene polymorphisms in Turkish rheumatoid arthritis patients

Toll-like receptors (TLRs) play an important role in the induction and regulation of the innate immune system or adaptive immune responses. Genetic variations within human TLRs have been reported to be associated with a range of immune-related diseases. This study was conducted to investigate the frequencies of TLR3 rs3775290, TLR9 rs187084, and TLR10 rs4129009 polymorphisms and to detect between polymorphisms and autoantibody positive as RF, collagen type II, anti-RNP, and anti-CCP in patient group. We performed a case–control study of 100 rheumatoid arthritis (RA) cases and 100 healthy controls matched on age, sex, and residence. All polymorphisms in TLRs were determined by polymerase chain reaction-based restriction fragment length polymorphism. Serum autoantibody level was measured using quantitative ELISA. SNPs were genotyped in all samples. Our results showed that TT genotype for SNP 1237 T/C increased the RA risk significantly (p < 0.05). No statistically significant differences were found in the TLR3 and TLR10 genotypes or allele distribution between RA patients and control individuals. No associations were noted with autoantibody production and TLR3, TLR9, and TLR10 polymorphisms genotypes (p > 0.05). Our study suggests that a single nucleotide polymorphism (rs187084) in TLR9 gene may be a susceptibility factor for RA in Turkish population. Further studies are required to explore the role of TLRs gene polymorphisms in the risk of RA, especially in ethnically different populations to confirm our results.     

TLR2, TLR4 and TLR9 polymorphisms and Crohn's disease in a New Zealand Caucasian cohort

BACKGROUND AND AIM: Toll-like receptors (TLRs) have been identified as susceptibility genes for Crohn's disease (CD) in some, but not all, studies. Here we examined the association between candidate disease-susceptibility polymorphisms in the TLR2, TLR4 and TLR9 genes and CD in a New Zealand Caucasian population. METHODS: The frequency of gene polymorphisms was examined in 182 CD patients and in 188 ethnically matched controls by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis. RESULTS: We could not detect any significant difference in the allele frequencies of polymorphisms in the TLR2 (R753Q, 0.029 vs 0.016, P = 0.25), TLR4 (D299G and T399I, 0.085 vs 0.071, P = 0.49; and 0.085 vs 0.082, P = 0.90), and TLR9 (-1237T/C, 0.154 vs 0.148, P = 0.82) genes between controls and patients, respectively. There was no evidence that the variant TLR alleles were associated with disease phenotype. However, combination of the datasets of published studies with our dataset confirmed that the TLR4 polymorphism 299G (P = 0.0005; OR of 1.42 [95% CI 1.17-1.74]) and the TLR9 polymorphism -1237C (P = 0.0416; OR of 1.33 [95% CI 1.01-1.75]) are associated with CD. CONCLUSIONS: There was no evidence that the above variants of the TLR2, TLR4 and TLR9 genes are major risk factors for CD or influence disease phenotype in our New Zealand case-control study. Nevertheless, the significance of the TLR4 299G and TLR9-1237C associations with CD worldwide was confirmed by a meta-analysis test using our datasets and datasets from previously published studies.     

Association of TLR4 gene non-missense single nucleotide polymorphisms with rheumatoid arthritis in Chinese Han population

Toll-like receptor4 (TLR4) plays an important role in the induction and regulation of the innate or adaptive immune responses. Thus, the genetic variation in TLR4 gene may influence the development of autoimmune diseases such as rheumatoid arthritis (RA). Several studies have investigated the roles of genetic polymorphisms of TLR4 gene in RA, but most of these studies were restricted to two cosegregating functional missense polymorphisms Asp299Gly and Thr399Ile. To determine whether non-missense genetic polymorphisms located in regulatory region of TLR4 are related to RA in a Chinese Han population, four single nucleotide polymorphisms (SNPs) situated on 3′ untranslating region (UTR) and 5′ UTR were genotyped in 213 RA patients and 247 unrelated ethnically matched controls using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and direct sequencing techniques. Significant genetic associations were observed with the 3′ UTR SNP rs41426344 and rs7873784. The minor allele C and homozygotic variant genotype CC of rs41426344 and minor allele C of rs7873784 were identified to be risk factors for the development of RA in Chinese Han people. Furthermore, by comparing the variation allele frequencies to other populations, prevalent genetic ethnic specificity was observed in all the four SNPs. Our study suggested that the effect of non-missense polymorphisms located in regulatory region would not be neglected in disease association analysis.     

Toll-like Receptor and Hepatitis B Virus Clearance in Chronic Infected Patients: A Long-Term Prospective Cohort Study in Taiwan

Background.We sought to elucidate the impacts of the Toll-like receptors (TLRs) on spontaneous hepatitis B virus (HBV) e antigen (HBeAg) and hepatitis B s antigen (HBsAg) seroconversion in chronic HBV-infected patients. Methods.Human TLR2, TLR4, TLR5, and TLR9 gene polymorphisms were assessed in 278 HBeAg-positive, chronic HBV-infected patients. Additionally, HBV core antigen (HBcAg) in vitro stimulation using peripheral blood mononuclear cells (PBMCs) from 113 patients was done to assess interferon γ (IFN- γ) production. Results.Of the study subjects, 204 (73.4%) developed spontaneous HBeAg seroconversion, 21 (7.6%) developed spontaneous HBsAg clearance, and 10 (3.6%) had spontaneous HBsAg seroconversion during the 19.1?±?9.9 years of follow-up. The T allele at TLR5 rs5744174 (p.Phe616Leu) and the C allele at TLR9 rs5743836 promoter predicted earlier HBeAg seroconversion (hazard ratios [HRs], 2.45 and 3.65; P?=?.04, and .006, respectively). The TLR5 rs5744174 T allele carriers have higher PBMCs IFN-γ secretion to HBcAg stimulation (P=?.0002). The G allele carriers at TLR4 rs4986790 (p.Asp299Gly) predicted spontaneous HBsAg seroclearance (HR, 18.73; P?相似文献   

Toll-like receptor polymorphisms and rheumatoid arthritis: a systematic review

The aim of this study was to determine whether toll-like receptor (TLR) polymorphisms confer susceptibility to rheumatoid arthritis (RA) and influence the clinical characteristics of RA. The authors conducted a systematic review on associations between TLR polymorphisms and RA susceptibility and clinical findings. Meta-analysis was performed if at least three comparisons of an issue were available. A total of 14 studies were included in this systematic review, which included European and Asian studies. Meta-analysis of five European studies showed no association between the TLR4 Asp299Gly (rs4986790) polymorphism and RA (OR for the minor allele = 0.907, 95 % CI = 0.755–1.088, p = 0.291). Furthermore, none of these studies found any association between the polymorphism and clinical characteristics. A significant difference between TLR9 rs187084 allele frequencies in RA patients and controls was found in one Turkish study (p = 0.003), and a moderate association between RF positivity and TLR8 rs5741883 was found in an European study (p = 0.001). The numbers of guanine–thymine [(GT)_n] repeats in intron II of the TLR2 gene were found a significantly higher S-allele frequency in Korean patients with RA than in controls (30.3 vs. 23.0 %, p = 0.03). This meta-analysis shows lack of an association between the TLR4 Asp299Gly polymorphism and RA. However, our finding suggests the possibility that TLR polymorphisms are associated with the development and clinical characteristics of RA. Because of a paucity of data of the TLR polymorphisms, case–control studies are required to determine whether TLR2, 4, 8, 9 polymorphisms contribute to RA susceptibility or severity in more than 2,000 patients and controls.     

Genetic variation in toll‐like receptors and retinoic acid‐inducible gene I and outcome of hepatitis C virus infection: a candidate gene association study

We evaluated the effects of genetic variation in toll‐like receptors (TLR), retinoic acid‐inducible gene I (RIG‐I) and their signalling pathways on spontaneous hepatitis C virus (HCV) resolution. We screened 95 single‐nucleotide polymorphisms (SNPs) in 22 genes. SNPs significantly associated with resolution in the discovery cohort were genotyped in a validation cohort. Multivariate logistic regression adjusted for sex, hepatitis B surface antigen, HIV infection and the interleukin‐28B rs12979860 SNP was performed in the combined cohort. Haplotype reconstruction and linkage disequilibrium analysis were performed. srs2233437, rs730775 and rs28362857 in Inhibitor of NF‐kB ε (IkBε) and rs352140 in TLR9 were associated with spontaneous HCV resolution (P ≤ 0.05) in the discovery cohort (n = 308). In the validation cohort (n = 216), we replicated a significant association with HCV resolution for two SNPs in the IkBε, rs2233437 and rs730775. Presence of one or two of the variant allele in rs2233437 had more than twofold higher odds of resolution in adjusted logistic regression (adjusted odds ratio (aOR), 2.6; (95% CI, 1.4, 4.8) P = 0.002). We identified polymorphisms in the IkBε gene associated with spontaneous HCV resolution in two independent cohorts.     

Association between Toll-like receptor 4 and inflammatory bowel disease

BACKGROUND: The human Toll-like receptor 4 (TLR4) participates in the innate response. Recently, the TLR4 variant Asp299Gly has been described to affect the response of this receptor to lipopolysaccharide. As such, there is a potentially important role of TLR4 in the pathogenesis of inflammatory bowel disease (IBD). We studied the involvement of TLR4 in IBD in a large population of Dutch patients with IBD and in family-based controls. METHODS: In 781 IBD cases and 315 controls, genotyping was performed forAsp299Gly and Thr399Ile variants and for 4 microsatellite markers flanking TLR4. Association analysis and the were applied. In addition, interaction of TLR4 with the caspase recruitment domain containing protein 15 gene (CARD15) was studied in patients with Crohn's disease (CD). RESULTS: The haplotype sharing statistic showed association at microsatellite marker D9S1864 with IBD (P = 0.0019), and in particular with CD (P = 0.0025) and at TLR406 with ulcerative colitis (UC; P = 0.027). No association was found for Asp299Gly and Thr399Ile. However, the frequencies of both variant allele carriers were higher among CD cases with a disease onset > or = 40 years than among controls. No evidence for interaction between TLR4 and CARD15 was found. CONCLUSIONS: Haplotype analysis shows that TLR4 is associated with both CD and UC. The Asp299Gly and Thr399Ile variants do not show an association with CD, UC, or IBD as a group, indicating that these polymorphisms are likely not the causal ones. We propose that the 2 polymorphisms are in linkage with (the) disease susceptibility variant(s) located elsewhere on TLR4.     

Association between <Emphasis Type="Italic">SLC2A9</Emphasis> (<Emphasis Type="Italic">GLUT9</Emphasis>) gene polymorphisms and gout susceptibility: an updated meta-analysis

The relationship between the SLC2A9 (solute carrier family 2, member 9) gene polymorphisms and gout was still inconsistent among the individual genetic association studies. Therefore, this present research was aimed to systematically evaluate the association between SLC2A9 gene polymorphisms and gout susceptibility. Relevant studies were enrolled by searching databases systematically. The pooled odds ratios (ORs) with 95 % confidence intervals (CIs) were used to assess the associations. The heterogeneity between each of the studies was calculated by using the Q statistic methods, and Begg’s funnel plot and Egger’s tests were performed to evaluate publication bias. A total of 13 studies investigated four single nucleotide polymorphisms (SNPs) in SLC2A9 were included. In this study, we found that the allele C of rs3733591 was higher in patients than in controls in both all-pooled population [C vs. T: OR (95 % CI) = 1.432 (1.213–1.691)] and Asians-pooled population [C vs. T: OR (95 % CI) = 1.583 (1.365–1.835)]. The allele frequency C of s6449213 was lower in the gout patients than in controls in both all-pooled population and Caucasians-pooled population. Additionally, the allele frequency T of rs16890979 and the allele frequency C of rs1014290 were lower in gout patients than in controls. This study demonstrated that the genetic susceptibility for gout is associated with the SLC2A9 gene polymorphisms. Four of them except for the rs3733591 are protective SNPs in Caucasians, and rs16890979 and rs1014290 are protective SNPs in both Caucasians and Asians, while rs3733591 may be susceptibility SNP in Asians.     

Toll样受体基因多态性与福建籍非人类免疫缺陷病毒相关隐球菌性脑膜炎易感性的关联分析

目的:探讨Toll样受体(Toll-like receptor,TLR)基因多态性与福建籍非人类免疫缺陷病毒(human immunodeficiency virus,HIV)相关隐球菌性脑膜炎易感性的关联。方法:纳入2016年10月至2019年4月在上海市复旦大学附属华山医院和福建省福州市联勤保障部队第九〇〇医院仓山院区住院治疗的101例福建籍非HIV相关隐球菌性脑膜炎患者为病例组,270名福建籍门诊健康体格检查者为健康对照组。提取患者基因组DNA,采用多重SNaPshot单核苷酸多态性(single nucleotide polymorphism,SNP)分型技术,对既往文献报道的与疾病相关但未得到充分验证的8个TLR SNP位点进行基因分型。分别比较病例组和健康对照组、无易感因素患者组和健康对照组TLR基因多态性的分布差异。统计学分析采用χ²检验或Fisher确切概率法。结果:除TLR1 rs5743563外,TLR1 rs5743604、TLR2 rs3804099、TLR4 rs1927907、TLR6 rs3796508、TLR6 rs5743794、TLR9 rs164637、TLR9 rs3521407个TLR SNP检测位点的等位基因频率分布均符合哈迪-温伯格平衡。病例组与健康对照组比较发现,TLR2 rs3804099位点的T/T基因型[52.5%(53/101)比40.4%(109/270),比值比(odds ratio,OR)=1.63,χ²=4.378,P=0.036]和TLR6 rs5743794位点的G/G基因型[44.6%(45/101)比32.2%(87/270),OR=1.69,χ²=4.877,P=0.027]为隐球菌性脑膜炎的风险基因型;而TLR6 rs3796508的G/G基因型[83.2%(84/101)比92.6%(250/270),OR=0.40,χ²=7.271,P=0.007]和TLR9 rs164637的C/C基因型[96.0%(97/101)比100.0%(270/270),Fisher确切概率法,P=0.005]为隐球菌性脑膜炎的保护性因素。101例患者中有70例无易感因素。无易感因素患者组与健康对照组比较发现,TLR6 rs5743794位点的G/G基因型[52.9%(37/70)比32.2%(87/270),OR=2.36,χ²=10.216,P=0.001]为隐球菌性脑膜炎的风险基因型,TLR6 rs3796508的G/G基因型[81.4%(57/70)比92.6%(250/270),OR=0.35,χ²=7.906,P=0.005]和TLR9 rs164637的C/C基因型[97.1%(68/70)比100.0%(270/270),Fisher确切概率法,P=0.042]为隐球菌性脑膜炎的保护性因素。结论:TLR基因多态性与福建籍非HIV相关隐球菌性脑膜炎的易感性密切关联,提示TLR在隐球菌性脑膜炎的发病过程中可能起到重要作用。     

Association study of Toll-like receptor 5 (TLR5) and Toll-like receptor 9 (TLR9) polymorphisms in systemic lupus erythematosus

OBJECTIVE: Toll-like receptors (TLR) play an important role in both adaptive and innate immunity. Variations in TLR genes have been shown to be associated with various infectious and inflammatory diseases. We investigated the association of TLR5 (Arg392Stop, rs5744168) and TLR9 (-1237T-->C, rs5743836) single nucleotide polymorphisms (SNP) with systemic lupus erythematosus (SLE) in Caucasian American subjects. METHODS: We performed a case-control association study and genotyped 409 Caucasian women with SLE and 509 Caucasian healthy female controls using TaqMan allelic discrimination (rs5744168) or polymerase chain reaction-restriction fragment length polymorphism analysis (rs5743836). RESULTS: None of the 2 TLR SNP showed a statistically significant association with SLE risk in our cohort. CONCLUSION: Our results do not indicate a major influence of these putative functional TLR SNP on the susceptibility to (or protection from) SLE.