The association of the immune response genes to human papillomavirus-related cervical disease in a Brazilian population.
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.
Campinas State University, Barão Geraldo, 13083878 Campinas, SP, Brazil.
Amanda Vansan
AV
Marangon
Gláucia Andreia Soares
GA
Guelsin
Jeane Eliete Laguila
JE
Visentainer
Sueli Donizete
SD
Borelli
Maria Angélica Ehara
MA
Watanabe
Márcia Edilaine Lopes
ME
Consolaro
Katiany Rizzieri
KR
Caleffi-Ferracioli
Cristiane Conceição Chagas
CC
Rudnick
Ana Maria
AM
Sell
D000483:Alleles; D001938:Brazil; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006680:HLA Antigens / Q000235:genetics; D006681:HLA-D Antigens / Q000235:genetics*; D006239:Haplotypes; D006801:Humans; D027383:Papillomaviridae / Q000235:genetics / Q000472:pathogenicity; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D024661:Potassium Channels, Inwardly Rectifying / Q000235:genetics*; D002578:Uterine Cervical Dysplasia / Q000235:genetics* / Q000276:immunology / Q000821:virology*
D006680:HLA Antigens; D006681:HLA-D Antigens; C086989:KCNJ1 protein, human; D024661:Potassium Channels, Inwardly Rectifying