RGD Reference Report - FOXP3 immunoregulatory gene variants are independent predictors of human papillomavirus infection and cervical cancer precursor lesions. - Rat Genome Database

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FOXP3 immunoregulatory gene variants are independent predictors of human papillomavirus infection and cervical cancer precursor lesions.

Authors: Cezar-Dos-Santos, Fernando  Ferreira, Rodolfo Sanches  Okuyama, Nádia Calvo Martins  Trugilo, Kleber Paiva  Sena, Michelle Mota  Pereira, Érica Romão  Pereira, Ana Paula Lombardi  Watanabe, Maria Angelica Ehara  de Oliveira, Karen Brajão 
Citation: Cezar-Dos-Santos F, etal., J Cancer Res Clin Oncol. 2019 Aug;145(8):2013-2025. doi: 10.1007/s00432-019-02951-x. Epub 2019 Jun 8.
RGD ID: 38501104
Pubmed: PMID:31177386   (View Abstract at PubMed)
DOI: DOI:10.1007/s00432-019-02951-x   (Journal Full-text)


PURPOSE: FOXP3 is a marker of the T regulatory (Treg) cell subset and drives its function and homeostasis. Its expression maintains the host immunosuppressive state that favors persistence of human papillomavirus (HPV) infection and squamous intraepithelial lesion (SIL) appearance. The present study evaluated the effects of the rs3761548 and rs2232365 intronic single-nucleotide variants (SNVs) and their haplotypes on HPV infection and SIL diagnosis in HPV-infected and -uninfected women.
METHODS: HPV DNA-based detection in cervical specimens was performed by PCR. FOXP3 variants were genotyped by PCR-restriction fragment length polymorphism and haplotype recombination sites were inferred for 208 HPV-infected and 218 HPV-uninfected women diagnosed or not with low- or high-grade intraepithelial lesions of cervix. Case-control analyses were carried out by logistic regression adjusted for several socio-demographic, sexual lifestyle, and clinical data.
RESULTS: The homozygous genotype of the rs3761548 variants (A/A) (related to decreased FOXP3 expression) may exert a protective role against HPV infection in women (ORAj: 0.60; 95% CI 0.36-0.99; p = 0.049) and was an independent predictor of protection against HSIL development (ORAdj: 0.28; 95% CI 0.11-0.68; p = 0.006). In addition, the homozygous genotype (G/G) of the rs2232365 variants (related to increased FOXP3 expression) was independently associated with the HPV infection (ORAdj: 2.10; 95% CI 1.06-4.15; p = 0.033). Haplotype analysis revealed no significant associations in our study.
CONCLUSIONS: Our results reveal the significant and independent associations between FOXP3 genetic variants and susceptibility to HPV infection and SIL diagnosis and their role as biomarkers of HPV infection and cervical lesion management.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
FOXP3Humanpapillomavirus infectious disease susceptibilityIAGP DNA:SNP::rs3761548(human)RGD 
Foxp3Mousepapillomavirus infectious disease susceptibilityISOFOXP3 (Homo sapiens)DNA:SNP::rs3761548(human)RGD 
Foxp3Ratpapillomavirus infectious disease susceptibilityISOFOXP3 (Homo sapiens)DNA:SNP::rs3761548(human)RGD 
FOXP3HumanSquamous Intraepithelial Lesions of the Cervix severityIAGP DNA:SNP::rs3761548(human)RGD 
Foxp3MouseSquamous Intraepithelial Lesions of the Cervix severityISOFOXP3 (Homo sapiens)DNA:SNP::rs3761548(human)RGD 
Foxp3RatSquamous Intraepithelial Lesions of the Cervix severityISOFOXP3 (Homo sapiens)DNA:SNP::rs3761548(human)RGD 

Objects Annotated

Genes (Rattus norvegicus)
Foxp3  (forkhead box P3)

Genes (Mus musculus)
Foxp3  (forkhead box P3)

Genes (Homo sapiens)
FOXP3  (forkhead box P3)


Additional Information