RESUMO
BACKGROUND: Periodontitis is a common oral disease caused by host inflammatory response towards bacteria biofilm. The chronic activation of immune response leads to destruction of teeth supporting tissue, bone loss and tooth detachment. Different factors could be involved in the development and severity of the disease; among them the host genetic background should be considered. OBJECTIVES: In our study, we analysed haploblocks in a genomic region within major histocompatibility complex (MHC) locus aimed at disclosing a possible correlation with the risk of periodontal disease in 602 adult subjects from North-East Italy. RESULTS: The CTTAC haploblock (formed by LTA-rs2857709, LTA-rs2844484, LTA- rs2229094, LTA-rs2229092 and LTA-rs1041981 polymorphisms) correlated with protection towards periodontitis condition, after regression analysis including age and smoking status as covariates (P-value = 0.015). CONCLUSION: Our results suggest that a haplotype within LTA gene (encoding for lymphotoxin alpha) is involved in the susceptibility towards chronic periodontitis.
Assuntos
Periodontite Crônica/genética , Estudos de Associação Genética , Predisposição Genética para Doença/genética , Genoma Humano/genética , Haploidia , Linfotoxina-alfa/genética , Complexo Principal de Histocompatibilidade/genética , Adulto , Idoso , Periodontite Crônica/imunologia , Periodontite Crônica/microbiologia , Feminino , Loci Gênicos/genética , Humanos , Inflamação , Itália , Masculino , Pessoa de Meia-Idade , Risco , Índice de Gravidade de DoençaRESUMO
We performed a retrospective genome-wide association study in HIV-infected individuals who were treated with dendritic cell-based immunotherapy in clinical trials performed by two research groups (Spain and Brazil). We aimed to identify host genetic variants influencing treatment response. The Illumina Human Core Exome 12 v 1.0 Bead Chip with over 250,000 markers was used to analyze genetic factors affecting treatment response. Additionally, we performed a meta-analysis of the results obtained from Spanish and Brazilian patients. We identified a genetic variation (rs7935564 G allele) in TRIM22 gene, which encodes TRIM22 protein acting like a HIV restriction factor, as being associated with good response to dendritic cell-based immunotherapy. We then verified the impact of TRIM22 rs7935564 SNP in susceptibility to HIV infection and disease progression by assessing the influence of biogeographic ancestry in the distribution of allelic and genotype frequencies in three populations from Italy, Brazil and Zambia. TRIM22 rs7935564 genotyping indicated association of G rs7935564 allele with long-term non-progression of HIV disease in Italian patients, thus corroborating our hypothesis that it is involved as a restriction factor in dendritic cell-based immunotherapy response. TRIM22 rs7935564 polymorphism was associated with good response to dendritic cell-based immunotherapy. We hypothesize that in selecting patients for treatment, there is a possible bias related to the natural presence of restriction factors that are genetically determined and could influence final outcome of therapy.