title: Role of inflammasome genetics in susceptibility to HPV infection and cervical cancer development.
abstract: Only a small proportion of HPV+ women develop virus-associated lesions and cervical cancer, suggesting that other factors are involved in HPV+ keratinocyte transformation. Immune response plays an important role in clearing HPV infection, and host genetic variants resulting in defective immune response have been associated with virus persistence and/or cervical cancer. Considering that genetic variations in inflammasome genes were previously associated with viral infection and cancer development, the present study investigates selected single nucleotide polymorphisms (SNPs) in inflammasome genes as a possible risk factor for HPV infection susceptibility and/or for progression to cervical cancer.
  
  
  
  12 SNPs in seven inflammasome-related genes (NLRP1, NLRP3, NLRP6, CARD8, IL1B, IL18, TNFAIP3) were genotyped in a Brazilian HPV+ case/control cohort (n = 246/310). Multivariate analysis was performed in case/control as well as in HPV+ women stratified by the presence or severity of histologic lesion, HPV persistence, and type of virus.
  
  
  
  IL1B rs1143643 was associated with protection against HPV infection in case/control analysis. NLRP1 rs11651270 plays a protection role against HPV persistence and/or oncogenesis. NLRP3 rs10754558 and IL18 rs1834481 exert a beneficial role against HPV persistence. NLRP3 rs10754558 variant resulted significantly associated with a lower risk to be infected with a high-risk HPV.
  
  
  
  Our findings for the first time demonstrated that inflammasome genetics could affect HPV/host interaction in terms of virus susceptibility as well as of virus/persistence and cervical cancer progression. J. Med. Virol. 88:1646-1651, 2016. © 2016 Wiley Periodicals, Inc.
authors.affiliation: Laboratory of Immunogenetics, Department of Immunology, Institute of Biomedical Sciences, University of Sao Paulo, Sao Paulo, SP, Brazil.
authors.forename: A
authors.initials: A
authors.lastname: Pontillo
authors.affiliation: Laboratory of Immunogenetics, Department of Immunology, Institute of Biomedical Sciences, University of Sao Paulo, Sao Paulo, SP, Brazil.
authors.forename: P
authors.initials: P
authors.lastname: Bricher
authors.affiliation: Laboratory of Immunogenetics, Department of Immunology, Institute of Biomedical Sciences, University of Sao Paulo, Sao Paulo, SP, Brazil.
authors.forename: V N C
authors.initials: VN
authors.lastname: Leal
authors.affiliation: Laboratory of Immunopathology "Keiko Azami", Federal University of Pernambuco, Recife, PE, Brazil.
authors.forename: S
authors.initials: S
authors.lastname: Lima
authors.affiliation: Department of Biology, Genetic Area, Federal Rural University of Pernambuco, Recife, PE, Brazil.
authors.forename: P R E
authors.initials: PR
authors.lastname: Souza
authors.affiliation: Department of Genetics, Federal University of Pernambuco, Recife, PE, Brazil.
authors.forename: S
authors.initials: S
authors.lastname: Crovella
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics; D000328:Adult; D051017:Apoptosis Regulatory Proteins / Q000235:genetics; D001938:Brazil / Q000453:epidemiology; D053468:CARD Signaling Adaptor Proteins / Q000235:genetics; D018450:Disease Progression; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D054884:Host-Pathogen Interactions; D006801:Humans; D058847:Inflammasomes / Q000235:genetics* / Q000276:immunology; D020382:Interleukin-18 / Q000235:genetics; D053583:Interleukin-1beta / Q000235:genetics; D008875:Middle Aged; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein / Q000235:genetics; D000070576:NLR Proteins; D009363:Neoplasm Proteins / Q000235:genetics; D030361:Papillomavirus Infections / Q000453:epidemiology / Q000276:immunology* / Q000821:virology; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D002583:Uterine Cervical Neoplasms / Q000276:immunology / Q000821:virology*; D002578:Uterine Cervical Dysplasia / Q000276:immunology / Q000821:virology
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D051017:Apoptosis Regulatory Proteins; D053468:CARD Signaling Adaptor Proteins; C455623:CARD8 protein, human; D058847:Inflammasomes; D020382:Interleukin-18; D053583:Interleukin-1beta; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; D000070576:NLR Proteins; C427903:NLRP1 protein, human; D009363:Neoplasm Proteins
keywords: HPV; IL-18; IL-1ß; NLRP3; inflammasome