人自然抵抗相关巨噬细胞蛋白1基因D543N和3''''UTR位点多态性与中国北方汉族成人肺结核易感性的关系

目的:探讨人自然抵抗相关巨噬细胞蛋白1基因D543N和3'UTR位点多态性与国内北方汉族成人肺结核发病的关系。方法:以2004-03/06唐山市结核病医院连续收治的汉族成人(年龄≥18岁)结核患者124例为研究对象,为病例组。同期通过健康查体的方式选择与病例组患者同民族、同性别、年龄相差<3岁,相同居住地(城市或农村),且经统一结核菌素试验确认为有结核分支杆菌感染的健康者为对照组。采用1∶1配对设计的病例对照观察。采用聚合酶链反应-限制性片段长度多态性分析检测人自然抵抗相关巨噬细胞蛋白1基因中D543N和3’UTR两个多态性位点,对肺结核相关的环境因素进行问卷调查,对肺结核的临床和病理进行分析,并进行单因素和多因素条件Logistic回归分析。结果:病例组124例,男83例,女41例;男性患者年龄(47±16)岁,女性(37±15)岁,男性患者发病年龄大于女性(P<0.05);农村患者75例,城市49例。对照组124例,男性年龄(47±15)岁,女性(38±12)岁,与病例组比较差异无显著性(P>0.05)。①D543N和3’UTR两个多态性位点的基因分型:D543NG/A,3’UTRTGTG /del基因型病例组频率显著高于对照组,其OR值(95%CI)分别为2.625(1.123～6.134),2.733(1.513～4.938)。②对17个环境危险因素进行单因素分析和多因素分析中,在调整卡痕、婚姻状况、体质量指数、接触史4个因素后,D543NG/A,3’UTRTGTG /del基因型仍与肺结核显著相关,调整OR值(95%CI)分别为3.151(1.225～8.105),3.306(1.517～7.201)。③在不同基因型中,病例组和对照组肺结核病变性质差异无显著性。结论:人自然抵抗相关巨噬细胞蛋白1基因D543N,3’UTR位点多态性可能是国内北方汉族成人肺结核的易感因素。     

中国海南黎族人群TAP1基因多态性与结核病的关联性研究

目的:研究海南黎族人群抗原处理相关转运体基因1(TAP1)多态性与肺结核病(PTB)易感性的关系。方法:应用PCR-RFLP技术对205例海南黎族肺结患者及217例海南黎族健康人群TAP1-1/TAP1-2(即Codon333/637)多态性进行检测。并对其易感性进行分析。结果:(1)海南黎族人群TAP1-1/TAP1-2基因多态性位点具有多态性(A→G);(2)TAP1-1Codon333多态性位点纯合型Val/VaL的基因频率病例组为4.88%,低于对照组5.33%,而病例组的杂合型Ile/Val频率为44.39%,明显高于对照组26.73%,在两组人群中,野生型Ile/Ile与杂合型比较,P=0.008,OR=1.92(95%CI:1.19～3.12),差异有意义,而与纯合型比较,无差异(P>0.05);(3)TAP1-2Codon637多态性位点纯合型Gly/Gly、杂合型Asp/Gly的基因频率在两组人群中的差异有高度显著性(P<0.01),其中野生型与杂合型比较OR=2.87(95%CI=1.75～4.71),与纯合型比较,OR=3.94,(95%CI=1.82～8.53)。结论:TAP1基因Codon637位点多态性可能是海南黎族人群肺结核的易感因素。     

人自然抵抗相关巨噬细胞蛋白1基因D543N和3’UTR位点多态性与中国北方汉族成人肺结核易感性的关系

目的：探讨人自然抵抗相关巨噬细胞蛋白1基因D543N和3＇UTR位点多态性与国内北方汉族成人肺结核发病的关系。 方法：以2004-03／06唐山市结核病医院连续收治的汉族成人（年龄≥18岁）结核患者124例为研究对象，为病例组。同期通过健康查体的方式选择与病例组患者同民族、同性别、年龄相差〈3岁，相同居住地（城市或农村），且经统一结核菌素试验确认为有结核分支杆菌感染的健康者为对照组。采用1：1配对设计的病例对照观察。采用聚合酶链反应-限制性片段长度多态性分析检测人自然抵抗相关巨噬细胞蛋白1基因中D543N和3’UTR两个多态性位点，对肺结核相关的环境因素进行问卷调查，对肺结核的临床和病理进行分析，并进行单因素和多因素条件Logistic回归分析。 结果：病例组124例，男83例，女41例；男性患者年龄（47&;#177;16）岁，女性（37&;#177;15）岁，男性患者发病年龄大于女性（P〈0．05）；农村患者75例，城市49例。对照组124例，男性年龄（47&;#177;15）岁，女性（38&;#177;12）岁，与病例组比较差异无显著性（P〉0．05）。①D543N和3’UTR两个多态性位点的基因分型：D543NG／A，3’UTR’TGTG＋／del基因型病例组频率显著高于对照组，其OR值（95％CI）分别为2．625（1．123～6．134）。2．733（1．513～4．938）。②对17个环境危险因素进行单因素分析和多因素分析中，在调整卡痕、婚姻状况、体质量指数、接触史4个因素后，D543NG／A，3’UTR TGTG＋／del基因型仍与肺结核显著相关，调整OR值（95％CI）分别为3．151（1．225-8．105），3．306（1．517-7．201）。③在不同基因型中，病例组和对照组肺结核病变性质差异无显著性。 结论：人自然抵抗相关巨噬细胞蛋白1基因D543N，3’UTR位点多态性可能是国内北方汉族成人肺结核的易感因素。     

HLA-G 3′UTR基因多态性及血清可溶性HLA-G水平与儿童诺如病毒感染的相关性研究

目的 探讨人类白细胞抗原-G(HLA-G)3′非翻译区(3′UTR)基因多态性(SNP)及血清可溶性HLA-G(sHLA-G)水平与儿童诺如病毒感染的相关性。方法 选取2021年1月至2022年12月新乡医学院第一附属医院收治的346例诺如病毒感染患儿作为病例组,另选取同期320例健康体检儿童作为对照组,留取所有研究对象全血标本并提取DNA。采用聚合酶链反应扩增HLA-G 3′UTR基因,产物外送测序。使用SNPstats在线分析软件计算两组间SNP位点基因型和等位基因分布频率。采用酶联免疫吸附试验检测病例组和对照组血清sHLA-G水平。结果 病例组和对照组HLA-G 3′UTR 14 bp+/-和+3142 C/G基因型和等位基因分布频率比较,差异均无统计学意义(P>0.05)。病例组血清sHLA-G水平明显高于对照组,差异有统计学意义(P<0.05);诺如病毒不同程度感染组血清sHLA-G水平比较,差异均无统计学意义(P>0.05)。病例组和对照组14 bp+/-基因型和+3142 C/G基因型对应的血清sHLA-G水平比较,差异均无统计学意义(P>0.05...     

364例蒙古族结核病患者易患基因多态性研究

目的探讨NRAMP1、Sp110基因多态性与蒙古族人群结核病易患性的关系。方法采用病例－对照研究，选取蒙古族结核病患者180例，正常体检者184例，应用聚合酶链式反应–限制性片段长度多态性（PCR-RFLP）方法检测NRAMP1、Sp110的基因型，计算各基因型在病例组和对照组的频率，采用χ2检验、logistic回归分析基因多态性与结核病易患性的关系。结果单因素χ2检验发现除体质指数（BMI）外其他因素在两组中分布均衡；NRAMP1rs17235409、NRAMP1rs17235416和Sp110rs3948464位点基因多态性均与结核易患性相关，3个位点突变基因型GA＋AA、TGTG/（－）＋（－）/（－）、CC结核病易患的危险度分别是未突变基因型GG、TGTG/TGTG、TT的1.784、4.745和3.061倍；BMI＜18.5是结核病易患的危险因素，其结核病易患的危险度是BMI≥18.5个体的4.350倍。结论NRAMP1rs17235409、NRAMP1rs17235416和Sp110rs3948464位点基因多态性与结核病易患有关。     

CTLA-4基因CT60标记与系统性红斑狼疮的相关性研究

目的研究细胞毒性T淋巴细胞相关抗原-4(CTLA-4)基因CT60标记与系统性红斑狼疮(SLE)的相关性。方法利用聚合酶链反应-限制性片段长度多态性分析(PCR-RFLP)对45例SLE患者和63名健康对照者进行CT60基因分型。采用荧光定量(FQ)-PCR法进行3′-非翻译区(3-′UTR)微卫星阵列(AT)n多态性基因分型,对CTLA-4基因3-′UTR微卫星阵列(AT)n与-1722T/C、-319C/T、+49A/G基因多态性进行分析,以求证CTLA-4单倍型与SLE的关系。结果在CT60A/G分型中,SLE患者AA基因型频率明显低于对照组(20.0%vs25.4%),P=0.003,校正后P(Pcorr)=0.009,优势比(odds ratio,OR)=0.58,95%CI 0.40~0.85。即病例组G基因表型频率高于对照组(80.0%vs74.6%),P=0.009,Pcorr=0.006,OR=1.71,95%CI 1.18~2.49。患者组与对照组的等位基因频率分布也明显不同(P=0.01),Pcorr=0.02,OR(等位基因G)=1.32,95%CI 1.06~1.65。结合不同基因多态性资料进行分析后,发现2个中性单倍型基因:+49A;(AT)7;CT60A和+49G;(AT)8~19;CT60G。此外,也发现易感性单倍型基因+49A;(AT)>19;CT60G。结论CTLA-4基因3-′UTR为SLE易感性基因片段。     

应用飞行时间质谱法研究甲型H1N1流感人群白细胞介素-1α基因单核苷酸多态性

探讨白细胞介素-1α(IL-1α)基因单核苷酸多态性(SNP)与甲型H1N1流感易感性的关系.方法:采用病例-对照研究方法,应用飞行时间质谱(time of flight mass spectrum)芯片技术,检测H1N1流感组(167例)和健康对照组(192例)IL-1α基因4个SNP位点(rs 1304037,rs16347,rs17561,rs2071373)多态性.结果:rs17561位点具有T和G两种等位基因,其中T等位基因频率在H1N1组为13.8％,对照组7.3％,差异具有统计学意义(P=0.004,OR=2.031,95％ CI 1.238-3.331);其他3个位点等位基因频率在两组人群中差异无统计学意义.结论:IL-1α基因rs17561位点多态性与甲型H1N1流感易感性相关,T等位基因是甲型H1N1流感易感基因.     

CD40-1C/T基因多态性与系统性红斑狼疮的相关性研究

目的研究CD40基因5’非翻译区(5’UTR)-1位点C/T单核苷酸多态性(SNP)在该地区系统性红斑狼疮(SLE)人群中的分布,探讨其与SLE的易感相关性。方法采用病例-对照研究方法,以107例门诊和住院SLE患者为研究对象,与109例正常对照组进行研究。应用聚合酶链反应-限制性内切酶片段长度多态性(PCR-RFLP)测定CD40基因-1位点C/T单核苷酸多态性,计算基因型及等位基因频率;同时将CD40基因-1C/T位点的三种基因型与SLE患者各种自身抗体检测结果进行比较。结果CD40基因-1C/T位点的基因型频率在SLE组和对照组中的分布差异有统计学显著性意义(P=0.035),其中SLE组的CC基因型频率明显高于对照组(OR值=2.020,P=0.016),CT基因型频率明显低于对照组(OR值=0.528,P=0.020);而等位基因频率分布差异无统计学意义(P=0.114)。SLE患者的抗RNP,抗SSA,抗SSB,抗dsDNA和抗组蛋白抗体在CC基因型中的阳性率最高。结论CD40基因5’非翻译区-1位点CC基因型可能与该地区SLE的发生有关。     

维生素D受体基因多态性与藏族儿童结核病易感性研究

目的探讨维生素D受体基因Fok I、BsmⅠ多态性与青藏高原藏族儿童结核病易感性的相关性。方法选取青海省妇女儿童医院2013-2015年的162例藏族儿童活动性肺结核患者作为病例组,167例有分枝杆菌接触史的同民族健康者作为对照组。采用聚合酶链反应-限制性片段长度多态性分析方法对两组研究对象进行维生素D受体基因FokⅠ、BsmⅠ多态性的检测,根据不同标本中分布结果进行统计学分析以研究两种多态性与青藏高原藏族儿童肺结核易感性的关系。结果病例组的FF、Ff与ff 3种基因型频率高于对照组,差异有统计学意义(P0.05,OR=2.692,95%CI:1.349~5.373)。病例组的BB、Bb、bb3种基因型与对照组的相应基因型频率差异无统计学意义(P0.05,OR=1.009,95%CI:0.560~1.816)。结论维生素D受体的FokⅠ多态性与高原藏族儿童肺结核易感性相关,其ff基因型可能是发病的风险因素,而与BsmⅠ多态性则无关。     

80例山西汉族先天性巨结肠症患儿RET基因单核苷酸多态性分析

目的研究80例山西汉族先天性巨结肠症(Hirschsprung disease,HSCR)患儿RET基因7、12、13、15号外显子的单核苷酸多态性(single nucleotides polymorphisms,SNPs)与HSCR发病的关系。方法通过测序及序列比对的方法,对山西省80例汉族散发性HSCR患者和80例汉族健康儿童进行RET基因外显子序列分析,比较基因多态性位点等位基因频率在两组的差异。结果 RET基因7号外显子A432A(GCA→GCG)位点存在多态性,病例组和对照组中该位点的等位基因分布频率存在显著性差异(χ2=5.668,P<0.05),风险等位基因为G等位基因,OR=3.05,95%可信区间为1.218～7.639;RET基因13号外显子L769L(CCT→CTA)位点存在多态性,病例组和对照组中该位点的等位基因分布频率存在显著差异(χ2=37.458,P<0.01),风险等位基因为G等位基因,OR=4.632,95%可信区间为2.832～7.577。7号外显子D489N(GAC→AAC),15号外显子S904S(TCC→TCG)存在多态位点,病例组与对照组中P>0.05,该位点与疾...     

新发和复发肺结核维生素D受体基因多态性分布

目的了解维生素D受体(VDR)基因多态性在中国汉族人群新发和复发肺结核中的分布情况,为探讨其与新发、复发肺结核的相关性打下基础。方法采用病例对照研究,选择新发、复发肺结核患者和健康对照者各30例,使用SNaPshot的SNP分型技术对以上入选者的VDR基因TaqI和FokI多态性位点进行检测分析。结果VDR基因FokI位点ff多态性在肺结核和对照组分布有差异(OR=6.53,95%CI:1.26~33.9,P=0.03);TaqI和FokI位点多态性在新发和复发肺结核中的分布差异无统计学意义(P>0.05)。结论VDR基因ff多态性与中国汉族肺结核易感性有关;TaqI和FokI位点多态性在新发和复发肺结核中的分布是否存在差异有待进一步研究。     

2016-2020年内蒙古自治区肺结核患者就诊延迟影响因素分析

目的 了解2016—2020年内蒙古自治区（内蒙古）肺结核患者就诊延迟情况,分析其影响因素,为制定相关防控措施,降低患者就诊延迟情况提供理论依据。方法 从《全民健康保障信息系统》中收集2016—2020年内蒙古肺结核患者登记信息,采用中位数及四分位间距描述进行统计描述,单因素和多因素logistic回归模型进行患者就诊延迟影响因素分析。结果 2016—2020年内蒙古肺结核患者就诊延迟天数中位数M(P25,P75)为32(11,67) d,年均就诊延迟率为70.80%(36 769/51 933),且就诊延迟率呈逐年下降趋势（χ2=335.552,P<0.001）;单因素分析结果显示,不同民族、年龄、户籍、职业、患者来源以及诊断结果分类患者组间就诊延迟率差异均有统计学意义（χ2=43.507、166.956、296.935、566.818、416.006、30.997,均P<0.001）,不同性别及治疗分类患者组间就诊延迟率差异无统计学意义（P=0.419、0.727）;多因素分析结果显示,少数民族、45～岁（<25岁年龄组为对照）、农民/牧民、离退人员、家务及待业人...     

Epidemiological and clinical features of 139 patients with tuberculosis at a teaching hospital in Italy (Pisa, 1996-2000).

In order to describe epidemiologic and clinical features of patients with tuberculosis (TB) identified recently in the hospital of Pisa (Tuscany, Italy), a retrospective study of all cases of TB notified to the Local Public Health Service during January 1996-December 2000 was performed. The diagnosis of TB was made following the criteria of the WHO. A total of 139 patients affected by TB were identified. Diagnosis was microbiologically proved in 81 patients. Mean age was 53.8+/-20.5 S.D. yrs. Thirty-five (25.2%) patients were extra European community citizens (mostly from Africa). The incidence of TB (N/100.000) was 8.4 in 1996 and 6.8 in 2000. Sixty-eight point three per cent of patients had pulmonary TB, 24.5% extrapulmonary and 7.2% mixed TB. The rate of extrapulmonary TB was 15.9% and 39.2% in the 1996-98 and in the 1999-2000 periods, respectively (p = 0.002). Extrapulmonary TB was more frequent in extra European community citizens (42.8%) than in Italian ones (18.3%), p = 0.003. Seven patients were presenting also advanced HIV infection. Microscopic examination for acid fast bacilli in sputum or bronchial secretion resulted negative in 17.4% of proved pulmonary TB (positive culture for Mycobacterium tuberculosis). The chest x-rays showed pleural effusion in 19 patients. Pulmonary cavitation was documented in 15 patients with negative chest x-rays. Fever was not present in 42.4% of the patients at the moment of diagnosis. Three point eight percent of the isolated strains of M. tuberculosis were in vitro multidrug-resistant. The data presented showed an important rate of TB in Pisa. We have yet to understand if the decreased rate observed in 2000 represents a new trend as reported in other North American and European countries. The rate of extrapulmonary TB shows a trend to increase accordingly to recent literature. The isolation rate of multidrug-resistant strains of M. tuberculosis in Pisa seems to be similar to the rates reported in other areas of Europe.     

Highlight on DPYD gene polymorphisms and treatment by capecitabine*

Abstract

Background: Sequencing of DPYD exome was conducted in a prospective cohort of advanced breast cancer patients receiving capecitabine.

Methods: A total of 243 patients were analyzed. Digestive, neurologic and hematotoxicity over cycles 1–2 showed 10.3% G3 and 2.1% G4, including one toxic death. DPYD exome, flanking intronic regions (20?bp), 3’UTR and part of 5’UTR (500?bp) were sequenced on MiSeq Illumina (Integragen, 97% coverage, HWE checked).

Results: In total, 48 SNPs were identified: three in 3’UTR, 19 in coding regions (four synonymous including E412E; 15 missenses including D949V, V732I, R592W, I560S, I543V, S534N, S492L, M406I, D342G, M166V, T65M, C29R), 19 in flanking intronic regions (including *2A) and seven in 5’UTR. In total, 11 SNPs have not been previously described, including three missense variations each heterozygous in three separate patients: R696H, F100L and A26T. The patient with a toxic death carried one D949V allele. The three consensual variants *2A, D949V and I560S were carried by seven patients (heterozygous). Analysis of consensual variants showed that they were associated with G3–4 toxicity (OR?=?21.0, sensitivity 16.7%) but not with G4 toxicity. Adding the variants previously associated with DPD deficiency in vitro, i.e. R592W, S492L and D342N/G, increased sensitivity on G3–4 (23.3%, OR?=?21.1) and was predictive of G4 toxicity (sensitivity 40%, OR?=?19.0). Of note, adding the new F100L variant further improved predictivity of genotyping on G4 toxicity (sensitivity 60%, OR?=?42.8).

Conclusions: Present data establish the impact of consensual variants on capecitabine toxicity and reveal the existence of a novel DPYD variant, F100L, associated with G4 toxicity.     

Correlation between lncRNA AC079767.4 variants and liver injury from antituberculosis treatment in West China

Antituberculosis drug-induced adverse drug reactions (ADRs) has been attached the increasing attention currently. And many host genetic determinants of ADRs have been identified. However, the possible relationship between long non-coding RNA (lncRNA) and ADRs is little investigated in tuberculosis (TB). We conducted a prospective survey and comprehensively collected the information of diverse ADRs during antituberculosis therapy. Next, we analyzed whether single nucleotide polymorphisms (SNPs) within lncRNA AC079767.4 gene are associated with ADRs development of patients with TB. Our results showed that the overall occurrence rate of ADRs due to TB treatment was 16.39% (70/427), of which the anti-tuberculosis drug-induced hepatotoxicity (ATDH) constituted the most common adverse events with prevalence rate of 12.88% (55/427). Notably, TB patients carrying T allele-containing genotypes in rs1055229 locus potentially presented a greater risk (1.85-fold, 95%CI = 1.04–3.28) for developing ATDH when compared with those CC genotype carriers, 17.28% versus. 10.19%, respectively, with the age- and gender -adjusted p-value of 0.035. Our data suggest that the ADRs exhibit serious morbidity in TB patients in West China, and for the first time we show that the AC079767.4 rs1055229 is a potential genetic risk component for ATDH development. Further studies on larger population and other ethnic groups are needed to confirm our results.     

Alpha-fetoprotein gene polymorphisms and risk of HCC and cirrhosis

BackgroundElevated level of alpha fetoprotein (AFP) is found in approximately 60% of hepatocellular carcinoma (HCC) cases. Other liver diseases including cirrhosis and chronic hepatitis are related with an increased level of AFP. The regulation of AFP gene expression has been relatively less studied although the gene has been suggested to play a role in HCC development. This study aimed at identifying genetic variations in AFP that might be associated with the presence of HCC and cirrhosis among ethnic Indonesians.MethodsDirect DNA sequencing was carried out to sequence AFP promoter, exons, and 3′ untranslated region (UTR) in DNA samples isolated from 119 HCC, 119 cirrhosis and 105 control subjects. For each sample serum AFP level was determined and association studies with single nucleotide polymorphisms (SNPs) and haplotypes were performed.ResultsIn this study we identified 47 SNPs in the AFP gene. Statistically significant associations with HCC and cirrhosis were detected for six individual SNPs in the AFP promoter, AFP intron 1 and intron 2 (rs6834059, rs3796678, rs3796677, rs3796676, rs28532518 and rs4646038). Furthermore, we identified two SNPs in AFP intron 7 and 3′UTR, rs2298839 and rs10020432, which are associated with increased risk of cirrhosis.ConclusionGenetic variants in the AFP gene may be associated with HCC and cirrhosis risk for ethnic Indonesians.     

C-reactive protein gene polymorphism 1009A>G is associated with serum CRP levels in Chinese men: a TCVGHAGE study

BACKGROUND: Increased concentrations of high-sensitivity CRP (hs-CRP) are associated with increased risk of cardiovascular disease. This increase might be caused by low-grade inflammation, but a number of studies have suggested that serum CRP concentrations are under genetic control. Since the relation between CRP concentration and cardiovascular diseases occurs across ethnicities, we determined whether CRP gene variants affect fasting hs-CRP concentrations in a cohort of Chinese men. METHODS: High-sensitivity CRP concentrations were measured in 369 Chinese men. Six polymorphisms were identified by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and direct sequencing within the CRP gene: 969T>C, 1009A>G, and a 3-allele polymorphism 1440C>A>T in the 5' UTR (promoter region), 2667G>C in exon 2, and 3872A>G and 5992T>A in the 3' UTR. RESULTS: In a group of participants (n=328) whose fasting serum hs-CRP concentrations were within the 5th to 95th percentile, we found that the genetic polymorphism 1009A>G was significantly associated with fasting serum hs-CRP concentrations (GG vs. AG or AA genotypes, CRP concentrations 0.072+/-0.062 vs. 0.176+/-0.166 and 0.166+/-0.185 mg/dl, mean+/-S.D., both P=0.023). Furthermore, subjects carrying the 1009G bearing haplotype exhibited the lowest CRP concentrations (P=0.05). CONCLUSION: The CRP 1009A>G genotypes and associated haplotypes were associated with lower fasting serum hs-CRP concentrations in a group of elderly Chinese men.     

Polymorphic Variation in TIRAP Is Not Associated with Susceptibility to Childhood TB but May Determine Susceptibility to TBM in Some Ethnic Groups

Host recognition of mycobacterial surface molecules occurs through toll like receptors (TLR) 2 and 6. The adaptor protein TIRAP mediates down stream signalling of TLR2 and 4, and polymorphisms in the TIRAP gene (TIRAP) have been associated with susceptibility and resistance to tuberculosis (TB) in adults. In order to investigate the role of polymorphic variation in TIRAP in childhood TB in South Africa, which has one of the highest TB incidence rates in the world, we screened the entire open reading frame of TIRAP for sequence variation in two cohorts of childhood TB from different ethnic groups (Xhosa and mixed ancestry). We identified 13 SNPs, including seven previously unreported, in the two cohorts, and found significant differences in frequency of the variants between the two ethnic groups. No differences in frequency between individual SNPs or combinations were found between TB cases and controls in either cohort. However the 558C→T SNP previously associated with TB meningitis (TBM) in a Vietnamese population was found to be associated with TBM in the mixed ancestry group. Polymorphisms in TIRAP do not appear to be involved in childhood TB susceptibility in South Africa, but may play a role in determining occurrence of TBM.