Genome, HLA and polygenic risk score analyses for prevalent and persistent cervical human papillomavirus (HPV) infections.
Journal
European journal of human genetics : EJHG
ISSN: 1476-5438
Titre abrégé: Eur J Hum Genet
Pays: England
ID NLM: 9302235
Informations de publication
Date de publication:
10 Jan 2024
10 Jan 2024
Historique:
received:
07
04
2023
accepted:
05
12
2023
revised:
22
09
2023
medline:
11
1
2024
pubmed:
11
1
2024
entrez:
10
1
2024
Statut:
aheadofprint
Résumé
Genetic variants that underlie susceptibility to cervical high-risk human papillomavirus (hrHPV) infections are largely unknown. We conducted discovery genome-wide association studies (GWAS), replication, meta-analysis and colocalization, generated polygenic risk scores (PRS) and examined the association of classical HLA alleles and cervical hrHPV infections in a cohort of over 10,000 women. We identified genome-wide significant variants for prevalent hrHPV around LDB2 and for persistent hrHPV near TPTE2, SMAD2, and CDH12, which code for proteins that are significantly expressed in the human endocervix. Genetic variants associated with persistent hrHPV are in genes enriched for the antigen processing and presentation gene set. HLA-DRB1*13:02, HLA-DQB1*05:02 and HLA-DRB1*03:01 were associated with increased risk, and HLA-DRB1*15:03 was associated with decreased risk of persistent hrHPV. The analyses of peptide binding predictions showed that HLA-DRB1 alleles that were positively associated with persistent hrHPV showed weaker binding with peptides derived from hrHPV proteins and vice versa. The PRS for persistent hrHPV with the best model fit, had a P-value threshold (PT) of 0.001 and a p-value of 0.06 (-log10(0.06) = 1.22). The findings of this study expand our understanding of genetic risk factors for hrHPV infection and persistence and highlight the roles of MHC class II molecules in hrHPV infection.
Identifiants
pubmed: 38200081
doi: 10.1038/s41431-023-01521-7
pii: 10.1038/s41431-023-01521-7
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : American Cancer Society (American Cancer Society, Inc.)
ID : RSG-22-079-01-CSCT
Investigateurs
Saurayya S Abdullahi
(SS)
Maryam Abdulsalam
(M)
Ruxton Adebiyi
(R)
Victor Adekanmbi
(V)
Bukunmi Adelekun
(B)
Segun Adeyemo
(S)
Gerald Akabueze
(G)
Bernice Akpobome
(B)
Stella Akpomiemie
(S)
Gabriel O Alabi
(GO)
Chinyere Anichebe
(C)
Claire Anyanwu
(C)
Miriam C Ayogu
(MC)
Dorcas J Bako
(DJ)
Patience Bamisaiye
(P)
Nkechi U Blessing
(NU)
Osa A Chinye
(OA)
Patrick Dakum
(P)
Eileen Dareng
(E)
Grace Dwana
(G)
Juliet I Erhunmwonsere
(JI)
Emelda O Eze
(EO)
Tolani A Fagbohun
(TA)
Temitope Filade
(T)
Toluwalope Gbolahan
(T)
Gloria C Anaedobe
(GC)
Stella Ibezim
(S)
Racheal Iwaloye
(R)
Jesse James
(J)
Dayo Kehinde
(D)
Fiyinfoluwa Makinde
(F)
Jessica Mase
(J)
Charles Mensah
(C)
Florence A Nwoko
(FA)
Kayode Obende
(K)
George Odonye
(G)
Folake Odubore
(F)
Funmi Odunyemi
(F)
Michael Odutola
(M)
Uzoamaka Oguama
(U)
Tochukwu Oguoma
(T)
Temitayo Oladimeji
(T)
Toyosi Olawande
(T)
Temitope Olukomogbon
(T)
Sefunmi Oluwole
(S)
Gladys Omenuko
(G)
Nkiruka Onwuka
(N)
Yinka Owoade
(Y)
Thelma C Ugorji
(TC)
Syntyche Yohanna
(S)
Ibrahim Yusuf
(I)
Informations de copyright
© 2024. The Author(s).
Références
Adebamowo SN, Olawande O, Famooto A, Dareng EO, Offiong R, Adebamowo CA, et al. Persistent low-risk and high-risk human papillomavirus infections of the uterine cervix in HIV-negative and HIV-positive women. Front Public Health. 2017;5:178.
pubmed: 28785554
pmcid: 5519520
doi: 10.3389/fpubh.2017.00178
de Martel C, Georges D, Bray F, Ferlay J, Clifford GM. Global burden of cancer attributable to infections in 2018: a worldwide incidence analysis. Lancet Glob Health. 2020;8:e180–e90.
pubmed: 31862245
doi: 10.1016/S2214-109X(19)30488-7
Dammann O, Dork T, Hillemanns P, Reydon T. Causation and causal inference in obstetrics-gynecology. Am J Obstet Gynecol. 2022;226:12–23.
pubmed: 34991897
doi: 10.1016/j.ajog.2021.09.047
Adebamowo SN, Adeyemo AA, Rotimi CN, Olaniyan O, Offiong R, Adebamowo CA, et al. Genome-wide association study of prevalent and persistent cervical high-risk human papillomavirus (HPV) infection. BMC Med Genet. 2020;21:231.
pubmed: 33225922
pmcid: 7682060
doi: 10.1186/s12881-020-01156-1
Famooto A, Almujtaba M, Dareng E, Akarolo-Anthony S, Ogbonna C, Offiong R, et al. RPS19 and TYMS SNPs and prevalent high risk human papilloma virus infection in Nigerian women. PLoS One. 2013;8:e66930.
pubmed: 23826176
pmcid: 3694982
doi: 10.1371/journal.pone.0066930
Wang SS, Gonzalez P, Yu K, Porras C, Li Q, Safaeian M, et al. Common genetic variants and risk for HPV persistence and progression to cervical cancer. PLoS One. 2010;5:e8667.
pubmed: 20084279
pmcid: 2801608
doi: 10.1371/journal.pone.0008667
Safaeian M, Hildesheim A, Gonzalez P, Yu K, Porras C, Li Q, et al. Single nucleotide polymorphisms in the PRDX3 and RPS19 and risk of HPV persistence and cervical precancer/cancer. PLoS One. 2012;7:e33619.
pubmed: 22496757
pmcid: 3322120
doi: 10.1371/journal.pone.0033619
Dilthey AT. State-of-the-art genome inference in the human MHC. Int J Biochem Cell Biol. 2021;131:105882.
pubmed: 33189874
doi: 10.1016/j.biocel.2020.105882
Adebamowo SN, Adeyemo AA, Consortium ARGapotHA. Classical HLA alleles are associated with prevalent and persistent cervical high-risk HPV infection in African women. Hum Immunol. 2019;80:723–30.
pubmed: 31072753
pmcid: 6773487
doi: 10.1016/j.humimm.2019.04.011
Luo Y, Kanai M, Choi W, Li X, Sakaue S, Yamamoto K, et al. A high-resolution HLA reference panel capturing global population diversity enables multi-ancestry fine-mapping in HIV host response. Nat Genet. 2021;53:1504–16.
pubmed: 34611364
pmcid: 8959399
doi: 10.1038/s41588-021-00935-7
Adebamowo SN, Dareng EO, Famooto AO, Offiong R, Olaniyan O, Obende K, et al. Cohort profile: African collaborative center for microbiome and genomics research’s (ACCME’s) human papillomavirus (HPV) and cervical cancer study. Int J Epidemiol. 2017;46:1745–j.
pubmed: 28419249
pmcid: 5837640
doi: 10.1093/ije/dyx050
Shang MM, Talukdar HA, Hofmann JJ, Niaudet C, Asl HF, Jain RK, et al. Lim domain binding 2: a key driver of transendothelial migration of leukocytes and atherosclerosis. Arterioscler Thromb Vasc Biol. 2014;34:2068–77.
pubmed: 24925974
doi: 10.1161/ATVBAHA.113.302709
Zhai D, Wang G, Li L, Jia X, Zheng G, Yin J. LIM-domain binding protein 2 regulated by m(6)A modification inhibits lung adenocarcinoma cell proliferation in vitro. Nan Fang Yi Ke Da Xue Xue Bao. 2021;41:329–35.
pubmed: 33849822
Grybko MJ, Bartnik JP, Wurth GA, Pores-Fernando AT, Zweifach A. Calcineurin activation is only one calcium-dependent step in cytotoxic T lymphocyte granule exocytosis. J Biol Chem. 2007;282:18009–17.
pubmed: 17478429
doi: 10.1074/jbc.M702222200
Mizuguchi T, Nakashima M, Kato M, Okamoto N, Kurahashi H, Ekhilevitch N, et al. Loss-of-function and gain-of-function mutations in PPP3CA cause two distinct disorders. Hum Mol Genet. 2018;27:1421–33.
pubmed: 29432562
doi: 10.1093/hmg/ddy052
Uhlen M, Fagerberg L, Hallstrom BM, Lindskog C, Oksvold P, Mardinoglu A, et al. Proteomics. Tissue-based map of the human proteome. Science. 2015;347:1260419.
pubmed: 25613900
doi: 10.1126/science.1260419
Braverman LE, Quilliam LA. Identification of Grb4/Nckbeta, a src homology 2 and 3 domain-containing adapter protein having similar binding and biological properties to Nck. J Biol Chem. 1999;274:5542–9.
pubmed: 10026169
doi: 10.1074/jbc.274.9.5542
UniProt C. UniProt: the universal protein knowledgebase in 2021. Nucleic Acids Res. 2021;49:D480–D9.
doi: 10.1093/nar/gkaa1100
Chaki SP, Barhoumi R, Rivera GM. Nck adapter proteins promote podosome biogenesis facilitating extracellular matrix degradation and cancer invasion. Cancer Med. 2019;8:7385–98.
pubmed: 31638742
pmcid: 6885876
doi: 10.1002/cam4.2640
Walker SM, Downes CP, Leslie NR. TPIP: a novel phosphoinositide 3-phosphatase. Biochem J. 2001;360:277–83.
pubmed: 11716755
pmcid: 1222227
doi: 10.1042/bj3600277
Worby CA, Dixon JE. Pten. Annu Rev Biochem. 2014;83:641–69.
pubmed: 24905788
doi: 10.1146/annurev-biochem-082411-113907
Christensen M, Najy AJ, Snyder M, Movilla LS, Kim HR. A critical role of the PTEN/PDGF signaling network for the regulation of radiosensitivity in adenocarcinoma of the prostate. Int J Radiat Oncol Biol Phys. 2014;88:151–8.
pubmed: 24331662
pmcid: 4920083
doi: 10.1016/j.ijrobp.2013.10.019
Lusche DF, Buchele EC, Russell KB, Soll BA, Vitolo MI, Klemme MR, et al. Overexpressing TPTE2 (TPIP), a homolog of the human tumor suppressor gene PTEN, rescues the abnormal phenotype of the PTEN(−/−) mutant. Oncotarget. 2018;9:21100–21.
pubmed: 29765523
pmcid: 5940379
doi: 10.18632/oncotarget.24941
Mishra RR, Chaudhary JK, Bajaj GD, Rath PC. A novel human TPIP splice-variant (TPIP-C2) mRNA, expressed in human and mouse tissues, strongly inhibits cell growth in HeLa cells. PLoS One. 2011;6:e28433.
pubmed: 22164291
pmcid: 3229583
doi: 10.1371/journal.pone.0028433
Lin X, Duan X, Liang YY, Su Y, Wrighton KH, Long J, et al. PPM1A functions as a Smad phosphatase to terminate TGFbeta signaling. Cell. 2006;125:915–28.
pubmed: 16751101
pmcid: 6309366
doi: 10.1016/j.cell.2006.03.044
Ki KD, Tong SY, Huh CY, Lee JM, Lee SK, Chi SG. Expression and mutational analysis of TGF-beta/Smads signaling in human cervical cancers. J Gynecol Oncol. 2009;20:117–21.
pubmed: 19590724
pmcid: 2704993
doi: 10.3802/jgo.2009.20.2.117
Iancu IV, Botezatu A, Goia-Rusanu CD, Stanescu A, Huica I, Nistor E, et al. TGF-beta signalling pathway factors in HPV-induced cervical lesions. Roum Arch Microbiol Immunol. 2010;69:113–8.
pubmed: 21434587
Haque PS, Apu MNH, Nahid NA, Islam F, Islam MR, Hasnat A, et al. SMAD2 rs4940086 heterozygosity increases the risk of cervical cancer development among the women in Bangladesh. Mol Biol Rep. 2020;47:5033–40.
pubmed: 32507921
doi: 10.1007/s11033-020-05572-7
Selig S, Bruno S, Scharf JM, Wang CH, Vitale E, Gilliam TC, et al. Expressed cadherin pseudogenes are localized to the critical region of the spinal muscular atrophy gene. Proc Natl Acad Sci USA. 1995;92:3702–6.
pubmed: 7731968
pmcid: 42029
doi: 10.1073/pnas.92.9.3702
Alimperti S, Andreadis ST. CDH2 and CDH11 act as regulators of stem cell fate decisions. Stem Cell Res. 2015;14:270–82.
pubmed: 25771201
pmcid: 4439315
doi: 10.1016/j.scr.2015.02.002
Zhao J, Li P, Feng H, Wang P, Zong Y, Ma J, et al. Cadherin-12 contributes to tumorigenicity in colorectal cancer by promoting migration, invasion, adhersion and angiogenesis. J Transl Med. 2013;11:288.
pubmed: 24237488
pmcid: 3879717
doi: 10.1186/1479-5876-11-288
Larue L, Ohsugi M, Hirchenhain J, Kemler R. E-cadherin null mutant embryos fail to form a trophectoderm epithelium. Proc Natl Acad Sci USA. 1994;91:8263–7.
pubmed: 8058792
pmcid: 44586
doi: 10.1073/pnas.91.17.8263
Radice GL, Rayburn H, Matsunami H, Knudsen KA, Takeichi M, Hynes RO. Developmental defects in mouse embryos lacking N-cadherin. Dev Biol. 1997;181:64–78.
pubmed: 9015265
doi: 10.1006/dbio.1996.8443
Vestweber D. Cadherins in tissue architecture and disease. J Mol Med (Berl). 2015;93:5–11.
pubmed: 25488198
doi: 10.1007/s00109-014-1231-5
Ma J, Zhao J, Lu J, Wang P, Feng H, Zong Y, et al. Cadherin-12 enhances proliferation in colorectal cancer cells and increases progression by promoting EMT. Tumour Biol. 2016;37:9077–88.
pubmed: 26762412
doi: 10.1007/s13277-015-4555-z
Noronha C, Ribeiro AS, Taipa R, Castro DS, Reis J, Faria C, et al. Cadherin expression and EMT: a focus on gliomas. Biomedicines. 2021;9:1328.
pubmed: 34680444
pmcid: 8533397
doi: 10.3390/biomedicines9101328
Jiang J, Li X, Yin X, Zhang J, Shi B. Association of low expression of E-cadherin and beta-catenin with the progression of early stage human squamous cervical cancer. Oncol Lett. 2019;17:5729–39.
pubmed: 31186799
pmcid: 6507444
Hu Y, Wu JZ, Zhu H, Zhang SH, Zhu YY, Wu YY, et al. Association of HLA-DRB1, HLA-DQB1 polymorphisms with HPV 16 E6 variants among young cervical cancer patients in China. J Cancer. 2017;8:2401–9.
pubmed: 28819444
pmcid: 5560159
doi: 10.7150/jca.19809
Cuzick J, Terry G, Ho L, Monaghan J, Lopes A, Clarkson P, et al. Association between high-risk HPV types, HLA DRB1* and DQB1* alleles and cervical cancer in British women. Br J Cancer. 2000;82:1348–52.
pubmed: 10755413
pmcid: 2374489
doi: 10.1054/bjoc.1999.1103
Bhaskaran M, Murali SV, Rajaram B, Krishnasamy S, Devasena CS, Pathak A, et al. Association of HLA-A, -B, DRB, and DQB alleles with persistent HPV-16 infection in women from Tamil Nadu, India. Viral Immunol. 2019;32:430–41.
pubmed: 31800372
doi: 10.1089/vim.2019.0094
de Araujo Souza PS, Maciag PC, Ribeiro KB, Petzl-Erler ML, Franco EL, Villa LL. Interaction between polymorphisms of the human leukocyte antigen and HPV-16 variants on the risk of invasive cervical cancer. BMC Cancer. 2008;8:246.
pubmed: 18721466
pmcid: 2546426
doi: 10.1186/1471-2407-8-246
Madeleine MM, Johnson LG, Smith AG, Hansen JA, Nisperos BB, Li S, et al. Comprehensive analysis of HLA-A, HLA-B, HLA-C, HLA-DRB1, and HLA-DQB1 loci and squamous cell cervical cancer risk. Cancer Res. 2008;68:3532–9.
pubmed: 18451182
pmcid: 2662593
doi: 10.1158/0008-5472.CAN-07-6471
Kamiza AB, Kamiza S, Mathew CG. HLA-DRB1 alleles and cervical cancer: a meta-analysis of 36 case-control studies. Cancer Epidemiol. 2020;67:101748.
pubmed: 32562888
doi: 10.1016/j.canep.2020.101748
Yang YC, Chang TY, Lee YJ, Su TH, Dang CW, Wu CC, et al. HLA-DRB1 alleles and cervical squamous cell carcinoma: experimental study and meta-analysis. Hum Immunol. 2006;67:331–40.
pubmed: 16720214
doi: 10.1016/j.humimm.2006.03.017
Wei LZ, Wang HL, Liu X, Lu YP, Xu F, Yuan JQ, et al. Meta-analysis on the relationship between HLA-DRBl gene polymorphism and cervical cancer in Chinese population. PLoS One. 2014;9:e88439.
pubmed: 24551099
pmcid: 3925111
doi: 10.1371/journal.pone.0088439
Bowden SJ, Bodinier B, Kalliala I, Zuber V, Vuckovic D, Doulgeraki T, et al. Genetic variation in cervical preinvasive and invasive disease: a genome-wide association study. Lancet Oncol. 2021;22:548–57.
pubmed: 33794208
pmcid: 8008734
doi: 10.1016/S1470-2045(21)00028-0
Adebamowo SN, Ma B, Zella D, Famooto A, Ravel J, Adebamowo C, et al. Mycoplasma hominis and mycoplasma genitalium in the vaginal microbiota and persistent high-risk human papillomavirus infection. Front Public Health. 2017;5:140.
pubmed: 28695118
pmcid: 5483445
doi: 10.3389/fpubh.2017.00140
Akarolo-Anthony SN, Al-Mujtaba M, Famooto AO, Dareng EO, Olaniyan OB, Offiong R, et al. HIV associated high-risk HPV infection among Nigerian women. BMC Infect Dis. 2013;13:521.
pubmed: 24192311
pmcid: 3826514
doi: 10.1186/1471-2334-13-521
Akarolo-Anthony SN, Famooto AO, Dareng EO, Olaniyan OB, Offiong R, Wheeler CM, et al. Age-specific prevalence of human papilloma virus infection among Nigerian women. BMC Public Health. 2014;14:656.
pubmed: 24972674
pmcid: 4094683
doi: 10.1186/1471-2458-14-656