Dataset Information

The association of the immune response genes to human papillomavirus-related cervical disease in a Brazilian population.

ABSTRACT: The genetic variability of the host contributes to the risk of human papillomavirus (HPV)-related cervical disease. Immune response genes to HPV must be investigated to define patients with the highest risk of developing malignant disease. The aim of this study was to investigate the association of polymorphic immune response genes, namely KIR, HLA class I and II, and single-nucleotide polymorphisms (SNPs) of cytokines with HPV-related cervical disease. We selected 79 non-related, admixed Brazilian women from the state of Paraná, southern region of Brazil, who were infected with high carcinogenic risk HPV and present cervical intraepithelial neoplasia grade 3 (CIN3), and 150 HPV-negative women from the same region matched for ethnicity. KIR genes were genotyped using an in-house PCR-SSP. HLA alleles were typed using a reverse sequence-specific oligonucleotide technique. SNPs of TNF -308G>A, IL6 -174G>C, IFNG +874T>A, TGFB1 +869T>C +915G>C, and IL10 -592C>A -819C>T -1082G>A were evaluated using PCR-SSP. The KIR genes were not associated with HPV, although some pairs of i(inhibitory)KIR-ligands occurred more frequently in patients, supporting a role for NK in detrimental chronic inflammatory and carcinogenesis. Some HLA haplotypes were associated with HPV. The associations of INFG and IL10 SNPs potentially reflect impaired or invalid responses in advanced lesions.

SUBMITTER: Marangon AV

PROVIDER: S-EPMC3722781 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

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The association of the immune response genes to human papillomavirus-related cervical disease in a Brazilian population.

Marangon Amanda Vansan AV Guelsin Gláucia Andreia Soares GA Visentainer Jeane Eliete Laguila JE Borelli Sueli Donizete SD Watanabe Maria Angélica Ehara MA Consolaro Márcia Edilaine Lopes ME Caleffi-Ferracioli Katiany Rizzieri KR Rudnick Cristiane Conceição Chagas CC Sell Ana Maria AM

BioMed research international 20130708

The genetic variability of the host contributes to the risk of human papillomavirus (HPV)-related cervical disease. Immune response genes to HPV must be investigated to define patients with the highest risk of developing malignant disease. The aim of this study was to investigate the association of polymorphic immune response genes, namely KIR, HLA class I and II, and single-nucleotide polymorphisms (SNPs) of cytokines with HPV-related cervical disease. We selected 79 non-related, admixed Brazil ...[more]

PMID: 23936772

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Project description:ImportanceBarriers to childhood vaccination against vaccine-preventable diseases, such as those due to human papillomavirus (HPV), are well known. However, the role of salience bias-the change in perception of risk due to increased familiarity with the outcome-in decisions to vaccinate children has not been explicitly studied.ObjectiveTo assess for salience bias in parental decisions to vaccinate children.Design, setting, and participantsThis retrospective cohort study used a time-to-event (survival) analysis to compare vaccination rates of children whose mothers had a history of cervical cancer or a cervical biopsy, who have experienced adverse vaccine-preventable outcomes, and for whom vaccination may be more salient, with a control group of children whose mothers had no such history. Participants were accrued from the MarketScan Commercial Database, including US children who turned 11 years old, when HPV vaccination is recommended, from January 1, 2014, to December 31, 2018. Data were analyzed from December 29, 2020, to September 17, 2021.ExposuresMaternal history of cervical cancer or cervical biopsy.Main outcomes and measuresVaccination against HPV.ResultsA total of 757 428 children (370 878 girls [49.0%] and 386 550 boys [51.0%]) were identified, of whom 38 366 had mothers with a history of cervical biopsy alone and 1084 had mothers with a history of cervical cancer. Overall, 54.2% of children (55.7% of girls and 52.7% of boys) received at least 1 vaccination by 16 years of age. In a time-to-event analysis, HPV vaccination did not differ between children whose mothers had cervical cancer vs those whose mothers did not (hazard ratio [HR] for girls, 0.99 [95% CI, 0.86-1.13]; HR for boys, 1.08 [95% CI, 0.94-1.24]). Maternal history of cervical biopsy was associated with a minimally increased hazard of vaccination (HR for girls, 1.06 [95% CI, 1.04-1.09]; HR for boys, 1.04 [95% CI, 1.01-1.06]). There were no clinically meaningful differences between groups for the tetanus/diphtheria/acellular pertussis and meningococcal vaccinations, which are also recommended at 11 years of age.Conclusions and relevanceIn this analysis of salience bias in childhood vaccination decisions, mothers' personal history of cervical cancer or cervical biopsy was not associated with greater vaccination rates among children against HPV. These findings suggest that salience of vaccine-preventable outcomes may not have a major impact on childhood vaccine hesitancy in HPV; the role of salience should be investigated for other vaccines.

Project description:SARS-CoV-2 utilizes the angiotensin-converting enzyme 2 (ACE2) receptor and transmembrane serine protease (TMPRSS2) to infect human lung cells. Previous studies have suggested that different host ACE2 and TMPRSS2 genetic backgrounds might contribute to differences in the rate of SARS-CoV-2 infection or COVID-19 severity. Recent studies have also shown that variants in 15 genes related to type I interferon immunity to influenza virus might predispose patients toward life-threatening COVID-19 pneumonia. Other genes (SLC6A20, LZTFL1, CCR9, FYCO1, CXCR6, XCR1, IL6, CTSL, ABO, and FURIN) and HLA alleles have also been implicated in the response to infection with SARS-CoV-2. Currently, Brazil has recorded the third-highest number of COVID-19 cases worldwide. We aimed to investigate the genetic variation present in COVID-19-related genes in the Brazilian population. We analyzed 27 candidate genes and HLA alleles in 954 admixed Brazilian exomes. We used the information available in two public databases (http://www.bipmed.org and http://abraom.ib.usp.br/) and additional exomes from individuals born in southeast Brazil, the region of the country with the highest number of COVID-19 patients. Variant allele frequencies were compared with the 1000 Genomes Project phase 3 (1KGP) and gnomAD databases. We detected 395 nonsynonymous variants; of these, 325 were also found in the 1KGP and/or gnomAD. Six of these variants were previously reported to influence the rate of infection or clinical prognosis of COVID-19. The remaining 70 variants were identified exclusively in the Brazilian sample, with a mean allele frequency of 0.0025. In silico analysis revealed that seven of these variants are predicted to affect protein function. Furthermore, we identified HLA alleles previously associated with the COVID-19 response at loci DQB1 and DRB1. Our results showed genetic variability common to other populations and rare and ultrarare variants exclusively found in the Brazilian population. These findings might lead to differences in the rate of infection or response to infection by SARS-CoV-2 and should be further investigated in patients with this disease.

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Dataset Information

The association of the immune response genes to human papillomavirus-related cervical disease in a Brazilian population.

Publications

The association of the immune response genes to human papillomavirus-related cervical disease in a Brazilian population.

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