Background: Cervix cancer is the leading cause of cancer death in women in many developing countries, and most commonly the result of human papillomavirus (HPV) infection. Most often, this infection does not lead to injury or cancer - there is viral clearance. We therefore proposed to study the polymorphism of certain genes such as KIR, which seems to have a strong association with HPV infection. We aimed to contribute to the fight against HPV virus infection, through better knowledge of circulating high risk-HPV (HR-HPV) genotype, and the involvement of KIR genes in the progression to cervical cancer. Methods: A total of 1419 samples, taken from the endocervix, were collected. The women came from 6 countries in West Africa (Burkina Faso, Benin, C？te d’Ivoire, Niger, Nigeria, and Togo). These samples were analyzed by multiplex real-time PCR to search for fourteen HR-HPV genotypes, and the KIR genes were characterized using the SSP-PCR method. Results: The results showed that 35.94% (510/1419) of women were infected with HR-HPV. KIR genes were significantly more common in HPV-infected subjects than in controls. The inhibitory KIR genes were, KIR 2DL3 [OR = 2.24, CI (95%) (1.48 - 3.39) p < 0.001], KIR 2DL4 [OR = 3.82, CI (95%) (1.77 - 8.23) p < 0.001], KIR 2DL5A [OR = 1.50, CI (95%) (1.05 - 2.15) p = 0.02], KIR 2DL5B [OR = 1.52, CI (95%) (1.07 - 2.17) p = 0.02], KIR 3DL2 [OR = 3.30, CI (95%) (1.29 - 8.47) p = 0.01] and the pseudogene KIR 2DP1 [OR = 1.97, CI (95%) (1.36 - 2.85) p < 0.001]. Conclusion: This study showed that the KIR genes 3DL3, 2DL4, 2DL5, 3DL2 and 2DP1 seems to be associated with the risk of developing HPV infection.
References
[1]
Cerwenka, A. and Lanier, L.L. (2001) Natural Killer Cells, Viruses and Cancer. Nature Reviews Immunology, 1, 41-49. https://doi.org/10.1038/35095564
[2]
Wilson, M.J., Torkar, M., Haude, A., Milne, S., Jones, T., Sheer, D., et al. (2000) Plasticity in the Organization and Sequences of Human KIR/ILT Gene Families. Proceedings of the National Academy of Sciences of the United States of America, 97, 4778-4783. https://doi.org/10.1073/pnas.080588597
[3]
Tembhurne, A.K., Maheshwari, A., Warke, H., Chaudhari, H., Kerkar, S.C., Deodhar, K., et al. (2022) Killer Cell Immunoglobulin‐like Receptor (KIR) Gene Contents: Are They Associated with Cervical Cancer? Journal of Medical Virology, 95, e27873. https://doi.org/10.1002/jmv.27873
[4]
Augusto, D.G. (2016) The Impact of KIR Polymorphism on the Risk of Developing Cancer: Not as Strong as Imagined? Frontiers in Genetics, 7, Article 121. https://doi.org/10.3389/fgene.2016.00121
[5]
Augusto, D.G., Lobo-Alves, S.C., Melo, M.F., Pereira, N.F. and Petzl-Erler, M.L. (2012) Activating KIR and HLA Bw4 Ligands Are Associated to Decreased Susceptibility to Pemphigus Foliaceus, an Autoimmune Blistering Skin Disease. PLOS ONE, 7, e39991. https://doi.org/10.1371/journal.pone.0039991
[6]
Augusto, D.G., Zehnder-Alves, L., Pincerati, M.R., Martin, M.P., Carrington, M. and Petzl-Erler, M.L. (2011) Diversity of the KIR Gene Cluster in an Urban Brazilian Population. Immunogenetics, 64, 143-152. https://doi.org/10.1007/s00251-011-0565-1
[7]
Hollenbach, J.A., Augusto, D.G., Alaez, C., Bubnova, L., Fae, I., Fischer, G., et al. (2012) 16th IHIW: Population Global Distribution of Killer Immunoglobulin-Like Receptor (KIR) and Ligands. International Journal of Immunogenetics, 40, 39-45. https://doi.org/10.1111/iji.12028
[8]
Norman, P.J., Carrington, C.V.F., Byng, M., Maxwell, L.D., Curran, M.D., Stephens, H.A.F., et al. (2002) Natural Killer Cell Immunoglobulin-Like Receptor (KIR) Locus Profiles in African and South Asian Populations. Genes & Immunity, 3, 86-95. https://doi.org/10.1038/sj.gene.6363836
[9]
Chandanayingyong, D., Vaughan, R.W., Verity, D.H., Norman, P.J. and Stephens, H.A.F. (2001) Distribution of Natural Killer Cell Immunoglobulin-Like Receptor Sequences in Three Ethnic Groups. Immunogenetics, 52, 195-205. https://doi.org/10.1007/s002510000281
[10]
González-Galarza, F.F., Takeshita, L.Y.C., Santos, E.J.M., Kempson, F., Maia, M.H.T., Silva, A.L.S.D., et al. (2014) Allele Frequency Net 2015 Update: New Features for HLA Epitopes, KIR and Disease and HLA Adverse Drug Reaction Associations. Nucleic Acids Research, 43, D784-D788. https://doi.org/10.1093/nar/gku1166
[11]
Arnheim, L., Dillner, J. and Sanjeevi, C.B. (2005) A Population-Based Cohort Study of kir Genes and Genotypes in Relation to Cervical Intraepithelial Neoplasia. Tissue Antigens, 65, 252-259. https://doi.org/10.1111/j.1399-0039.2005.00359.x
[12]
Brestovac, B., Harnett, G.B., Smith, D.W., Shellam, G.R. and Frost, F.A. (2005) Human Papillomavirus Genotypes and Their Association with Cervical Neoplasia in a Cohort of Western Australian Women. Journal of Medical Virology, 76, 106-110. https://doi.org/10.1002/jmv.20330
[13]
Brestovac, B., Wong, M.E., Tjendera, R., Costantino, P.J., Mamotte, C. and Witt, C.S. (2013) Human Papillomavirus, High-Grade Intraepithelial Neoplasia and Killer Immunoglogulin-Like Receptors: A Western Australian Cohort Study. Infectious Agents and Cancer, 8, Article No. 33. https://doi.org/10.1186/1750-9378-8-33
[14]
Mhandire, K., Zijenah, L.S., Yindom, L., Duri, K., Mlambo, T., Tshabalala, M., et al. (2016) KIR Gene Content Diversity in a Zimbabwean Population: Does KIR2DL2 Have a Role in Protection against Human Immunodeficiency Virus Infection? OMICS: A Journal of Integrative Biology, 20, 727-735. https://doi.org/10.1089/omi.2016.0154
[15]
Naranbhai, V., de Assis Rosa, D., Werner, L., Moodley, R., Hong, H., Kharsany, A., et al. (2015) Killer-Cell Immunoglobulin-Like Receptor (KIR) Gene Profiles Modify HIV Disease Course, Not HIV Acquisition in South African Women. BMC Infectious Diseases, 16, Article No. 27. https://doi.org/10.1186/s12879-016-1361-1
[16]
Sorgho, A.P., Martinson, J.J., Djigma, F.W., Yonli, A.T., Nagalo, B.M., Compaore, R.T., et al. (2018) Insights into the Interplay between KIR Gene Frequencies and Chronic HBV Infection in Burkina Faso. Mediterranean Journal of Hematology and Infectious Diseases, 10, e2018060. https://doi.org/10.4084/mjhid.2018.060
[17]
Yindom, L., de Silva, T.I. and Rowland-Jones, S.L. (2015) Identification of a Novel Three-Domain KIR Allele: KIR3DL1*087 Using High-Resolution Molecular Techniques. Tissue Antigens, 85, 153-154. https://doi.org/10.1111/tan.12502
[18]
Yindom, L., de Silva, T.I. and Rowland-Jones, S.L. (2015) KIR3DL1*0250102: A Novel Three-Domain KIR Subtype Identified in West Africa. Tissue Antigens, 85, 151-152. https://doi.org/10.1111/tan.12501
[19]
Leone, P., De Re, V., Vacca, A., Dammacco, F. and Racanelli, V. (2017) Cancer Treatment and the KIR-HLA System: An Overview. Clinical and Experimental Medicine, 17, 419-429. https://doi.org/10.1007/s10238-017-0455-4
[20]
Ilboudo, R., et al. (2020) Prevalence and Characterization of High-Risk Human Papilloma-Virus Genotypes among a Group of Sex Workers in Ouagadougou, Burkina Faso. EC Gynaecology, 9, 1-9.
[21]
Djigma, F.W., Ouédraogo, C., Karou, D.S., Sagna, T., Bisseye, C., Zeba, M., et al. (2011) Prevalence and Genotype Characterization of Human Papillomaviruses among HIV-Seropositive in Ouagadougou, Burkina Faso. Acta Tropica, 117, 202-206. https://doi.org/10.1016/j.actatropica.2010.12.007
[22]
Ouedraogo, C.M., et al. (2015) [Epidemiology and Characterization of High-Risk Genotypes of Human Papillomavirus in a Population of Sexually Active Adolescents in Ouagadougou]. Journal de Gynécologie Obstétrique et Biologie de la Reproduction (Paris), 44, 715-722.
[23]
Ouedraogo, R.A., Zohoncon, T.M., Guigma, S.P., Angèle Traore, I.M., Ouattara, A.K., Ouedraogo, M., et al. (2018) Oncogenic Human Papillomavirus Infection and Genotypes Characterization among Sexually Active Women in Tenkodogo at Burkina Faso, West Africa. Papillomavirus Research, 6, 22-26. https://doi.org/10.1016/j.pvr.2018.09.001
[24]
Prosper, B., Florencia, D.W., Mahoukèdè, Z.T., Dorcas, O., Alima, T.E.M., Karim, O.A., et al. (2020) Polymorphism of MMP1 and MMP3 Promoter Regions and HR-HPV Infection in Women from Burkina Faso and Côte d’Ivoire. Biomolecular Concepts, 11, 116-124. https://doi.org/10.1515/bmc-2020-0010
[25]
Traore, I.M.A., Zohoncon, T.M., Dembele, A., Djigma, F.W., Obiri-Yeboah, D., Traore, G., et al. (2016) Molecular Characterization of High-Risk Human Papillomavirus in Women in Bobo-Dioulasso, Burkina Faso. BioMed Research International, 2016, Article ID: 7092583. https://doi.org/10.1155/2016/7092583
[26]
Traore, I.M.A., Zohoncon, T.M., Ndo, O., Djigma, F.W., Obiri-Yebo, D., Compaore, T.R., et al. (2016) Oncogenic Human Papillomavirus Infection and Genotype Characterization among Women in Orodara, Western Burkina Faso. Pakistan Journal of Biological Sciences, 19, 306-311. https://doi.org/10.3923/pjbs.2016.306.311
[27]
Zohoncon, T.M. and Simpore, J. (2013) Prevalence of HPV High-Risk Genotypes in Three Cohorts of Women in Ouagadougou (Burkina Faso). Mediterranean Journal of Hematology and Infectious Diseases, 5, e2013059. https://doi.org/10.4084/mjhid.2013.059
[28]
Zohoncon, T.M., Ouedraogo, T.C., Brun, L.V.C., Obiri-Yebo, D., Djigma, W.F., Kabibou, S., et al. (2016) Molecular Epidemiology of High-Risk Human Papillomavirus in High-Grade Cervical Intraepithelial Neoplasia and in Cervical Cancer in Parakou, Republic of Benin. Pakistan Journal of Biological Sciences, 19, 49-56. https://doi.org/10.3923/pjbs.2016.49.56
[29]
Zohoncon, T.M.B., et al. (2016) Molecular Characterization of High-Risk Human Papillomavirus Genotypes Involved in Invasive Cervical Cancer from Formalin-Fixed, Paraffin-Embedded Tissues in Ouagadougou, Burkina Faso. International Journal of Current Research, 8, 39314-39318.
[30]
Salambanga, C., et al. (2019) High Prevalence of High-Risk Human Papillomavirus (HPV) Infection among Sexually Active Women in Ouagadougou. Médecine et Santé Tropicales, 29, 302-305.
[31]
Lanier, L.L. (2005) NK CELL Recognition. Annual Review of Immunology, 23, 225-274. https://doi.org/10.1146/annurev.immunol.23.021704.115526
[32]
Contreras, G., Aláez, C., Murguía, A., García, D., Flores, H. and Gorodezky, C. (2007) Distribution of the Killer Cell Immunoglobulin-Like Receptors in Mexican Mestizos. Tissue Antigens, 69, 125-129. https://doi.org/10.1111/j.1399-0039.2006.76212.x
[33]
Augusto, D.G., Norman, P.J., Dandekar, R. and Hollenbach, J.A. (2019) Fluctuating and Geographically Specific Selection Characterize Rapid Evolution of the Human KIR Region. Frontiers in Immunology, 10, Article 989. https://doi.org/10.3389/fimmu.2019.00989
[34]
Denis, L., Sivula, J., Gourraud, P.‐., Kerdudou, N., Chout, R., Ricard, C., et al. (2005) Genetic Diversity of KIR Natural Killer Cell Markers in Populations from France, Guadeloupe, Finland, Senegal and Réunion. Tissue Antigens, 66, 267-276. https://doi.org/10.1111/j.1399-0039.2005.00473.x
[35]
Nakimuli, A., Chazara, O., Farrell, L., Hiby, S.E., Tukwasibwe, S., Knee, O., et al. (2013) Killer Cell Immunoglobulin-Like Receptor (KIR) Genes and Their HLA-C Ligands in a Ugandan Population. Immunogenetics, 65, 765-775. https://doi.org/10.1007/s00251-013-0724-7
[36]
Gentle, N.L., Loubser, S., Paximadis, M., Puren, A. and Tiemessen, C.T. (2017) Killer-cell Immunoglobulin-Like Receptor (KIR) and Human Leukocyte Antigen (HLA) Class I Genetic Diversity in Four South African Populations. Human Immunology, 78, 503-509. https://doi.org/10.1016/j.humimm.2017.05.006
[37]
Bani, M., Seket, J., Kaabi, H., Cherif, G., Chaabane, M., Bellali, H., et al. (2015) Killer Cell Immunoglobulin-Like Receptor (KIR) Locus Profiles in the Tunisian Population. Human Immunology, 76, 355-361. https://doi.org/10.1016/j.humimm.2015.03.002
[38]
Marangon, A.V., Guelsin, G.A.S., Visentainer, J.E.L., Borelli, S.D., Watanabe, M.A.E., Consolaro, M.E.L., et al. (2013) The Association of the Immune Response Genes to Human Papillomavirus-Related Cervical Disease in a Brazilian Population. BioMed Research International, 2013, Article ID: 146079. https://doi.org/10.1155/2013/146079
[39]
Song, M.J., Lee, C.W., Kim, J.H., Lee, S.J., Kim, C.J., Hur, S.Y., et al. (2013) Association of KIR Genes and HLA-C Alleles with HPV-Related Uterine Cervical Disease in Korean Women. Tissue Antigens, 81, 164-170. https://doi.org/10.1111/tan.12068
[40]
Rizzo, R., Gentili, V., Rotola, A., Bortolotti, D., Cassai, E. and Di Luca, D. (2014) Implication of HLA-C and KIR Alleles in Human Papillomavirus Infection and Associated Cervical Lesions. Viral Immunology, 27, 468-470. https://doi.org/10.1089/vim.2014.0017
