Tumor necrosis factor (TNF) alpha and interleukin (IL) 18 genes polymorphisms are correlated with susceptibility to HPV infection in patients with and without cervical intraepithelial lesion

• Published in: Annals of human biology Vol. 43; no. 3; pp. 261 - 268
• Main Authors: Tavares, Mayara C. Mansur, de Lima Júnior, Sérgio F., Coelho, Antonio V. C., Marques, Trícia Ruschelle N. M., de Araújo, Diêgo Henrique T., Heráclio, Sandra de A., Amorim, Melânia M. Ramos, de Souza, Paulo Roberto E., Crovella, Sergio
• Format: Journal Article
• Language: English
• Published: England Taylor & Francis 03-05-2016
• Subjects: Adolescent; Adult; Aged; Cervical Intraepithelial Neoplasia - genetics; Cervical Intraepithelial Neoplasia - virology; Cytokine; Female; Genetic Predisposition to Disease; Humans; Interleukin-18 - genetics; invasive cervical cancer; Middle Aged; Papillomaviridae - physiology; Papillomavirus Infections - genetics; Papillomavirus Infections - virology; Polymorphism, Single Nucleotide - genetics; single nucleotide polymorphism; Tumor Necrosis Factor-alpha - genetics; Uterine Cervical Neoplasms - genetics; Uterine Cervical Neoplasms - virology; Young Adult; single nucleotide polymorphism; invasive cervical cancer; Cytokine
• ISSN: 0301-4460; 1464-5033
• DOI: 10.3109/03014460.2014.1001436

Background: The Human Papillomavirus (HPV) predisposes 500 000 women to cervical cancer. Host genetic background may facilitate virus persistence in the uterine cervix. Polymorphisms in regulatory and coding regions of cytokine genes have been associated with susceptibility to some human diseases.
Aim: This study aims at investigating whether TNFA -308 G/A and IL18 -137 G/C and -607 C/A polymorphisms are associated with susceptibility to HPV infection/progression to high-grade squamous intraepithelial lesion (HSIL).
Subjects and methods: One hundred and twenty-two HPV infected and 132 HPV negative women (the latter used as healthy controls) were analysed. TNFA -308 G/A and IL18 (-137G/C and -607 C/A) polymorphisms were analysed using specific sequence polymorphism PCR (SSP-PCR). Univariate statistical analysis and a logistic regression were performed.
Results: The TNFA -308A allele was associated with susceptibility to HPV infection (p = 0.0008), while the IL18 -607A allele conferred protection against HPV infection (p = 0.0043). TNFA -308 G/A and IL18 (-137G/C and -607 C/A) polymorphisms were not associated with development of cervical lesions (p > 0.05). An association was also observed between smoking and susceptibility to the development of HSIL.
Conclusion: The findings suggest an association between two TNFA SNPs and susceptibility to HPV infection in women from Northeast Brazil. The results need to be functionally validated and replicated in other populations with different ethnic backgrounds.