Polymorphisms in TLR4 and TNFA and Risk of Mycobacterium tuberculosis Infection and Development of Active Disease in Contacts of Tuberculosis Cases in Brazil: A Prospective Cohort Study

被引：20

作者：

Cubillos-Angulo, Juan Manuel ^{[1
,2
,3
]}

Arriaga, Maria B. ^{[1
,2
,3
]}

Silva, Elisangela C. ^{[4
,5
,6
]}

Mueller, Beatriz L. A. ^{[4
,5
,7
]}

Ramalho, Daniela M. P. ^{[4
,5
]}

Fukutani, Kiyoshi F. ^{[1
,3
]}

Miranda, Pryscila F. C. ^{[4
,5
]}

Moreira, Adriana S. R. ^{[4
,5
]}

Ruffino-Netto, Antonio ^{[8
]}

Lapa e Silva, Jose R. ^{[4
,5
]}

Sterling, Timothy R. ^{[9
]}

Kritski, Afranio L. ^{[4
,5
]}

Oliveira, Martha M. ^{[10
]}

Andrade, Bruno B. ^{[1
,3
,9
,11
,12
,13
]}

机构：

[1] Fundacao Oswaldo Cruz, Inst Goncalo Moniz, Salvador, BA, Brazil

[2] Univ Fed Bahia, Fac Med, Salvador, BA, Brazil

[3] Fundacao Jose Silveira, Multinat Org Network Sponsoring Translat & Epidem, Salvador, BA, Brazil

[4] Univ Fed Rio de Janeiro, Fac Med, Programa Acad TB, Rio De Janeiro, Brazil

[5] Univ Fed Rio de Janeiro, Complexo Hosp HUCFF IDT, Rio De Janeiro, Brazil

[6] State Univ North Fluminense Darcy Ribeiro, Ctr Biosci & Biotechnol, Recognize Biol Lab, Campos Dos Goytacazes, RJ, Brazil

[7] Fiocruz MS, Inst Oswaldo Cruz, Lab Genom Func & Bioinformat, Rio De Janeiro, Brazil

[8] Univ Sao Paulo, Fac Med Ribeirao Preto, Sao Paulo, Brazil

[9] Vanderbilt Univ, Sch Med, Dept Med, Div Infect Dis, Nashville, TN 37212 USA

[10] Fundacao Oswaldo Cruz, Ctr Desenvolvimento Tecnol Saude, Rio De Janeiro, Brazil

[11] Univ Cape Town, Wellcome Ctr Infect Dis Res Africa, Inst Infect Dis & Mol Med, Rondebosch, South Africa

[12] Laureate Univ, Univ Salvador UNIFACS, Baltimore, MD USA

[13] Escola Bahiana Med & Saude Publ, Salvador, BA, Brazil

来源：

CLINICAL INFECTIOUS DISEASES | 2019年 / 69卷 / 06期

基金：

美国国家卫生研究院;

关键词：

single-nucleotide polymorphism; tuberculin skin test; Mycobacterium tuberculosis; tumor necrosis factor; Toll-like receptor; PULMONARY TUBERCULOSIS; GENE POLYMORPHISMS; SUSCEPTIBILITY; ASSOCIATION; EXPRESSION;

D O I：

10.1093/cid/ciy1001

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

Background. The role of genetic polymorphisms in latent tuberculosis (TB) infection and progression to active TB is not fully understood. Methods. We tested the single-nucleotide polymorphisms (SNPs) rs5743708 (TLR2), rs4986791 (TLR4), rs361525 (TNFA), rs2430561 (IFNG) rs1143627 (IL1B) as risk factors for tuberculin skin test (TST) conversion or development of active TB in contacts of active TB cases. Contacts of microbiologically confirmed pulmonary TB cases were initially screened for longitudinal evaluation up to 24 months, with clinical examination and serial TST, between 1998 and 2004 at a referral center in Brazil. Data and biospecimens were collected from 526 individuals who were contacts of 177 active TB index cases. TST conversion was defined as induration >= 5 mm after a negative TST result (0 mm) at baseline or month 4 visit. Independent associations were tested using logistic regression models. Results. Among the 526 contacts, 60 had TST conversion and 44 developed active TB during follow-up. Multivariable regression analysis demonstrated that male sex (odds ratio [OR]: 2.3, 95% confidence interval [CI]: 1.1-4.6), as well as SNPs in TLR4 genes (OR: 62.8, 95% CI: 7.5-525.3) and TNFA (OR: 4.2, 95% CI: 1.9-9.5) were independently associated with TST conversion. Moreover, a positive TST at baseline (OR: 4.7, 95% CI: 2.3-9.7) and SNPs in TLR4 (OR: 6.5, 95% CI: 1.1-36.7) and TNFA (OR: 12.4, 95% CI:5.1-30.1) were independently associated with incident TB. Conclusions. SNPs in TLR4 and TNFA predicted both TST conversion and active TB among contacts of TB cases in Brazil.

引用

页码：1027 / 1035

页数：9