title: Association of MBL2, TLR1, TLR2 and TLR6 Polymorphisms With Production of IFN-γ and IL-12 in BCG Osteitis Survivors R1.
abstract: Interferon-gamma (IFN-γ) is a key cytokine in defense against mycobacteria, including Bacillus Calmette-Guérin (BCG). Mannose-binding lectin (MBL) and toll-like receptors (TLRs) are pattern-recognizing molecules of innate immunity. The aim of the present study was to investigate the relationship between polymorphisms in MBL, TLR1, TLR2 and TLR6 encoding genes and stimulated IFN-γ and interleukin-12 (IL-12) ex vivo production in BCG osteitis survivors.
  
  
  
  Data on single nucleotide polymorphisms in the MBL2 gene and TLR1, TLR2 and TLR6 genes were available from 132 former BCG osteitis patients, and data on ex vivo IFN-γ and IL-12 production were available from 115 and 118 patients, respectively. The present study is a secondary analysis of these available data. In an earlier study, we were able to characterize low IFN-γ and low IL-12 producers after BCG+IL-12 or BCG+IFN-γ stimulations, respectively.
  
  
  
  Three patients had the homozygous variant MBL2 genotype, and one of them was a low IFN-γ producer (both concentration and response <5th percentile). The heterozygous variant MBL2 genotype showed no association with IFN-γ or IL-12 production. The TLR2 variant genotype was present in 14 subjects; 28.6% of them were low IFN-γ producers versus 7.8% of those 103 with the TLR2 wild genotype (P = 0.037). TLR1 or TLR6 polymorphisms had no significant associations with stimulated ex vivo IFN-γ or IL-12 production.
  
  
  
  Preliminary evidence was found that variant genotypes of the MBL2 gene (if homozygous) and variant genotypes of the TLR2 gene (only heterozygotes present) are associated with low IFN-γ production.
authors.affiliation: From the *Center for Child Health Research, University of Tampere and University Hospital, Tampere, Finland; †Department of Pediatrics, University Hospital, Kuopio, Finland; ‡School of Health Sciences, University of Tampere, Tampere, Finland; §Department of Infectious Disease Surveillance and Control, National Institute for Health and Welfare, Turku, Finland; ¶Department of Pediatrics, Seinäjoki Central Hospital, Seinäjoki, Finland; ‖Department of Pediatrics, University of Turku and University Hospital, and **Department of Medical Microbiology and Immunology, University of Turku, Turku, Finland.
authors.forename: Laura
authors.initials: L
authors.lastname: Pöyhönen
authors.forename: Liisa
authors.initials: L
authors.lastname: Kröger
authors.forename: Heini
authors.initials: H
authors.lastname: Huhtala
authors.forename: Johanna
authors.initials: J
authors.lastname: Mäkinen
authors.forename: Kirsi
authors.initials: K
authors.lastname: Nuolivirta
authors.forename: Jussi
authors.initials: J
authors.lastname: Mertsola
authors.forename: Qiushui
authors.initials: Q
authors.lastname: He
authors.forename: Matti
authors.initials: M
authors.lastname: Korppi
mesh_terms: D000328:Adult; D001500:BCG Vaccine / Q000009:adverse effects*; D001850:Bone Diseases, Infectious / Q000235:genetics*; D015331:Cohort Studies; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics; D006801:Humans; D007371:Interferon-gamma / Q000097:blood*; D018664:Interleukin-12 / Q000097:blood*; D008297:Male; D037601:Mannose-Binding Lectin / Q000235:genetics*; D008875:Middle Aged; D009163:Mycobacterium bovis; D010000:Osteitis / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D051193:Toll-Like Receptors / Q000235:genetics*; D014376:Tuberculosis / Q000235:genetics; D055815:Young Adult
chemical_list: D001500:BCG Vaccine; C445619:MBL2 protein, human; D037601:Mannose-Binding Lectin; D051193:Toll-Like Receptors; D018664:Interleukin-12; D007371:Interferon-gamma