title: Toll-like receptor 1(TLR1) Gene SNP rs5743618 is associated with increased risk for tuberculosis in Han Chinese children.
abstract: Toll-like receptor 1 (TLR1) recognizes lipopeptides with TLR2, and affects immune response to Mycobacterium tuberculosis infection. Here, we report results of the first case-control pediatric study of the TLR1 single-nucleotide polymorphisms and susceptibility to tuberculosis (TB). A pediatric case-control study enrolled 340 TB patients and 366 healthy controls, all Han Chinese from North China. Significant differences of the allelic and genotypic distributions of rs5743618 in TLR1 gene were observed between TB group and control group and, G allele of rs5743618 was associated with increased risk for TB (OR: 2.40, 95%CI: 1.41-4.07, P = 0.0009). TLR1 rs5743618 -GT genotype was related to reduction in surface expression of TLR1 in monocytes and granulocytes regardless of stimulation with inactivated H37Rv. In addition, after stimulated with inactivated lysate of M. tuberculosis strain H37Rv, samples of peripheral blood mononuclear cells (PBMCs) from children with the rs5743618 GT genotypes showed a decreased level of Tumor Necrosis Factor-a (TNF-a) and CXC chemokine ligand 10 (CXCL10) production, invariable production of interleukin-6 (IL-6) and IL-8 and increased production of IL-10 ex vivo. To conclude, TLR1 rs5743618 G allele was found associated to susceptibility to TB in Han Chinese pediatric population. TLR1 rs5743618-GT genotype carriers may have reduced immune response to MTB infection although further study is warranted to test this conclusion.
authors.affiliation: Key Laboratory of Major Diseases in Children and National Key Discipline of Pediatrics (Capital Medical University), Ministry of Education, Beijing Key Laboratory of Pediatric Respiratory Infection Diseases, Beijing Pediatric Research Institute, Beijing Children's Hospital, Capital Medical University, No. 56 Nan-li-shi Road, Beijing 100045, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Qi
authors.affiliation: Key Laboratory of Major Diseases in Children and National Key Discipline of Pediatrics (Capital Medical University), Ministry of Education, Beijing Key Laboratory of Pediatric Respiratory Infection Diseases, Beijing Pediatric Research Institute, Beijing Children's Hospital, Capital Medical University, No. 56 Nan-li-shi Road, Beijing 100045, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Sun
authors.affiliation: Key Laboratory of Major Diseases in Children and National Key Discipline of Pediatrics (Capital Medical University), Ministry of Education, Beijing Key Laboratory of Pediatric Respiratory Infection Diseases, Beijing Pediatric Research Institute, Beijing Children's Hospital, Capital Medical University, No. 56 Nan-li-shi Road, Beijing 100045, China.
authors.forename: Xirong
authors.initials: X
authors.lastname: Wu
authors.affiliation: Key Laboratory of Major Diseases in Children and National Key Discipline of Pediatrics (Capital Medical University), Ministry of Education, Beijing Key Laboratory of Pediatric Respiratory Infection Diseases, Beijing Pediatric Research Institute, Beijing Children's Hospital, Capital Medical University, No. 56 Nan-li-shi Road, Beijing 100045, China.
authors.forename: Yaqiong
authors.initials: Y
authors.lastname: Jin
authors.affiliation: Key Laboratory of Major Diseases in Children and National Key Discipline of Pediatrics (Capital Medical University), Ministry of Education, Beijing Key Laboratory of Pediatric Respiratory Infection Diseases, Beijing Pediatric Research Institute, Beijing Children's Hospital, Capital Medical University, No. 56 Nan-li-shi Road, Beijing 100045, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Xiao
authors.affiliation: Department of Epidemiology and Bio-statistics, School of Public Health, Peking University Health Science Center, Beijing 100191, China.
authors.forename: Shengfeng
authors.initials: S
authors.lastname: Wang
authors.affiliation: Key Laboratory of Major Diseases in Children and National Key Discipline of Pediatrics (Capital Medical University), Ministry of Education, Beijing Key Laboratory of Pediatric Respiratory Infection Diseases, Beijing Pediatric Research Institute, Beijing Children's Hospital, Capital Medical University, No. 56 Nan-li-shi Road, Beijing 100045, China.
authors.forename: Chen
authors.initials: C
authors.lastname: Shen
authors.affiliation: Key Laboratory of Major Diseases in Children and National Key Discipline of Pediatrics (Capital Medical University), Ministry of Education, Beijing Key Laboratory of Pediatric Respiratory Infection Diseases, Beijing Pediatric Research Institute, Beijing Children's Hospital, Capital Medical University, No. 56 Nan-li-shi Road, Beijing 100045, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Chu
authors.affiliation: Key Laboratory of Major Diseases in Children and National Key Discipline of Pediatrics (Capital Medical University), Ministry of Education, Beijing Key Laboratory of Pediatric Respiratory Infection Diseases, Beijing Pediatric Research Institute, Beijing Children's Hospital, Capital Medical University, No. 56 Nan-li-shi Road, Beijing 100045, China.
authors.forename: Zhan
authors.initials: Z
authors.lastname: Qi
authors.affiliation: Key Laboratory of Major Diseases in Children and National Key Discipline of Pediatrics (Capital Medical University), Ministry of Education, Beijing Key Laboratory of Pediatric Respiratory Infection Diseases, Beijing Pediatric Research Institute, Beijing Children's Hospital, Capital Medical University, No. 56 Nan-li-shi Road, Beijing 100045, China.
authors.forename: Fang
authors.initials: F
authors.lastname: Xu
authors.affiliation: Key Laboratory of Major Diseases in Children and National Key Discipline of Pediatrics (Capital Medical University), Ministry of Education, Beijing Key Laboratory of Pediatric Respiratory Infection Diseases, Beijing Pediatric Research Institute, Beijing Children's Hospital, Capital Medical University, No. 56 Nan-li-shi Road, Beijing 100045, China.
authors.forename: Yajie
authors.initials: Y
authors.lastname: Guo
authors.affiliation: Key Laboratory of Major Diseases in Children and National Key Discipline of Pediatrics (Capital Medical University), Ministry of Education, Beijing Key Laboratory of Pediatric Respiratory Infection Diseases, Beijing Pediatric Research Institute, Beijing Children's Hospital, Capital Medical University, No. 56 Nan-li-shi Road, Beijing 100045, China.
authors.forename: Weiwei
authors.initials: W
authors.lastname: Jiao
authors.affiliation: Key Laboratory of Major Diseases in Children and National Key Discipline of Pediatrics (Capital Medical University), Ministry of Education, Beijing Key Laboratory of Pediatric Respiratory Infection Diseases, Beijing Pediatric Research Institute, Beijing Children's Hospital, Capital Medical University, No. 56 Nan-li-shi Road, Beijing 100045, China.
authors.forename: Jianling
authors.initials: J
authors.lastname: Tian
authors.affiliation: Key Laboratory of Major Diseases in Children and National Key Discipline of Pediatrics (Capital Medical University), Ministry of Education, Beijing Key Laboratory of Pediatric Respiratory Infection Diseases, Beijing Pediatric Research Institute, Beijing Children's Hospital, Capital Medical University, No. 56 Nan-li-shi Road, Beijing 100045, China. Electronic address: shenad16@hotmail.com.
authors.forename: Adong
authors.initials: A
authors.lastname: Shen
mesh_terms: D016022:Case-Control Studies; D002478:Cells, Cultured; D054357:Chemokine CXCL10 / Q000096:biosynthesis; D002648:Child; D002675:Child, Preschool; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006098:Granulocytes / Q000276:immunology; D006801:Humans; D007223:Infant; D007378:Interleukins / Q000096:biosynthesis; D008297:Male; D009000:Monocytes / Q000276:immunology; D020641:Polymorphism, Single Nucleotide; D051194:Toll-Like Receptor 1 / Q000235:genetics* / Q000378:metabolism; D014376:Tuberculosis / Q000235:genetics* / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
chemical_list: C114753:CXCL10 protein, human; D054357:Chemokine CXCL10; D007378:Interleukins; D051194:Toll-Like Receptor 1; D014409:Tumor Necrosis Factor-alpha
keywords: Pediatric tuberculosis; Polymorphism; Toll-like receptor 1