Laboratory of Immunogenetics, Department of Immunology, Institute of Biomedical Sciences, University of Sao Paulo, Sao Paulo, SP, Brazil.
Laboratory of Immunopathology "Keiko Azami", Federal University of Pernambuco, Recife, PE, Brazil.
J Med Virol. 2016 Sep;88(9):1646-51. doi: 10.1002/jmv.24514. Epub 2016 Apr 20.
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.
只有一小部分 HPV+ 女性会发展为病毒相关病变和宫颈癌，这表明其他因素也参与了 HPV+ 角质形成细胞的转化。免疫反应在清除 HPV 感染中起着重要作用，而导致免疫反应缺陷的宿主遗传变异与病毒持续存在和/或宫颈癌有关。鉴于炎症小体基因的遗传变异先前与病毒感染和癌症发展有关，本研究调查了炎症小体基因中选定的单核苷酸多态性（SNP）是否可能成为 HPV 感染易感性和/或进展为宫颈癌的风险因素。
在巴西 HPV+ 病例对照队列（n=246/310）中，对七个炎症小体相关基因（NLRP1、NLRP3、NLRP6、CARD8、IL1B、IL18、TNFAIP3）中的 12 个 SNP 进行了基因分型。在病例对照以及按组织学病变的存在或严重程度、HPV 持续存在和病毒类型分层的 HPV+ 女性中进行了多变量分析。
IL1B rs1143643 与病例对照分析中的 HPV 感染保护相关。NLRP1 rs11651270 对 HPV 持续存在和/或致癌作用起到保护作用。NLRP3 rs10754558 和 IL18 rs1834481 对 HPV 持续存在具有有益作用。NLRP3 rs10754558 变体与感染高危 HPV 的风险降低显著相关。
我们的研究结果首次表明，炎症小体遗传学可能影响 HPV/宿主相互作用，包括病毒易感性以及病毒/持续性和宫颈癌进展。医学病毒学杂志 88:1646-1651,2016。©2016 威利父子公司
