Role of inflammasome genetics in susceptibility to HPV infection and cervical cancer development.

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.

Pontillo A ，Bricher P ，Leal VN ，Lima S ，Souza PR ，Crovella S ... -  《-》

Genotyping and differential expression analysis of inflammasome genes in sporadic malignant melanoma reveal novel contribution of CARD8, IL1B and IL18 in melanoma susceptibility and progression.

Sporadic melanoma malignancy is correlated with constitutive secretion of IL-1β in transformed melanocytes suggesting the involvement of inflammasome in melanoma. Common variants in inflammasome genes are known to affect IL-1β expression. To investigate the contribution of inflammasome genetics in melanoma development and progression and to identify a potential prognostic marker, the distribution of selected inflammasome SNPs was analysed in a Brazilian case/control cohort of sporadic malignant melanoma (SMM) and then the expression of inflammasome components was evaluated in melanoma biopsies. Allele and gene-specific Taqman assays were implied for genotyping of case/control DNA samples and for relative expression analysis in skin biopsies respectively. CARD8 rs6509365 was found to be significantly more common in healthy volunteers than in SMM patients suggesting a protection effect of this variant towards melanoma development. Accordingly, CARD8 expression was found to be reduced in nevus compared to melanoma biopsies. Upon stratification, NLRP1 rs11651270 and CARD8 rs2043211 were found associated with nodular melanoma; IL1B rs1143643 to a lower value of Breslow index; IL18 rs5744256 to melanoma development in sun sensitive individuals. As expected, IL1B expression was up-regulated in tumour biopsies especially in metastatic samples, whereas IL18 was down-regulated compared to nevus. Our results demonstrated for the first time the contribution of inflammasome genes CARD8, IL1B and IL18 in SMM.

da Silva WC ，Oshiro TM ，de Sá DC ，Franco DD ，Festa Neto C ，Pontillo A ... -  《Cancer Genetics》

Polymorphisms and expression of inflammasome genes are associated with the development and severity of rheumatoid arthritis in Brazilian patients.

Addobbati C ，da Cruz HLA ，Adelino JE ，Melo Tavares Ramos AL ，Fragoso TS ，Domingues A ，Branco Pinto Duarte ÂL ，Oliveira RDR ，Louzada-Júnior P ，Donadi EA ，Pontillo A ，de Azevêdo Silva J ，Crovella S ，Sandrin-Garcia P ... -  《-》

Polymorphisms in inflammasome' genes and susceptibility to HIV-1 infection.

Pontillo A ，Oshiro TM ，Girardelli M ，Kamada AJ ，Crovella S ，Duarte AJ ... -  《-》

Inflammasome genes polymorphisms may influence the development of hepatitis C in the Amazonas, Brazil.

Toro DM ，Ramasawmy R ，Silva Neto PV ，Pereira GL ，Sarmento PS ，Dray HLSN ，Sousa KS ，Affonso JS ，Silva JA ，Garcia NP ，Barbieri MV ，Victória FS ，Donadi EA ，Costa AG ，Ogusku MM ，Sadahiro A ，Tarragô AM ，Malheiro A ... -  《PLoS One》