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1.
Eur J Hum Genet ; 32(6): 708-716, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38200081

ABSTRACT

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.


Subject(s)
Genome-Wide Association Study , HLA-DRB1 Chains , Papillomavirus Infections , Humans , Female , Papillomavirus Infections/virology , Papillomavirus Infections/genetics , HLA-DRB1 Chains/genetics , Multifactorial Inheritance , Genetic Predisposition to Disease , HLA-DQ beta-Chains/genetics , Alleles , Papillomaviridae/genetics , Polymorphism, Single Nucleotide , Risk Factors , Uterine Cervical Neoplasms/virology , Uterine Cervical Neoplasms/genetics , Adult , Genetic Risk Score , Human Papillomavirus Viruses
2.
PLoS One ; 17(3): e0265269, 2022.
Article in English | MEDLINE | ID: mdl-35353833

ABSTRACT

BACKGROUND: There are limited data on the epidemiology of HPV in different anatomical sites of female sex workers (FSW). We investigated the prevalence and concordance of cervical, vulval, oral and anal HPV among FSW in Ibadan, Nigeria. METHODS: FSWs aged 18-45 years were enrolled in a cross-sectional survey. After interview and clinical examination, samples were collected from mouth, cervix, vulva and anus. HPV genotyping was done with Anyplex II 28HPV assay. Multivariable analyses were performed to explore associated risk factors and concordance of HPV infections across sites. RESULTS: In total, 315 FSWs participated in the study with a mean age of 30-6.5 years. The prevalence of any HPV infection was 88% in the vulva, 84% in the cervix, 75% in the anus and 24% in the oral cavity. HPV 35 was the most prevalent and concordant high-risk type in the four sites. The risk factors for HPV infection by anatomic site varied. CONCLUSION: This large study showed a high prevalence and concordance of HPV infections of cervical, vulval, oral and anal HPV among FSWs in Nigeria. The potential to acquire and transmit HPV is high in this population, and we highlighted the urgency to protect young women through HPV vaccination.


Subject(s)
Papillomavirus Infections , Sex Workers , Anal Canal , Cross-Sectional Studies , Female , Genitalia , Humans , Nigeria/epidemiology , Papillomaviridae/genetics , Papillomavirus Infections/epidemiology , Prevalence
4.
Article in English | MEDLINE | ID: mdl-18984975

ABSTRACT

BACKGROUND AND PURPOSE: Despite the increasing occurrence of suppurative otitis media (SOM), the content of immunoglobulin fractions in the middle ear secretion (MES) has still not been determined. METHOD: The serum and MESwere analyzed for IgG and M using enzyme-linked immunoassay. RESULT: The subjects and controls were 30 males and 22 females, between 6 months and 9 years old, with a mean age of 6 years (SD = 3.26). The patient group included 20 chronic SOM (CSOM) and 17 acute SOM (ASOM) cases, and sera of 15 subjects made the control group. The mean serum IgG levels were for controls 1,051 mg/dl, ASOM 666.1 mg/dl and CSOM 1,321.1 mg/dl; the MES levels were for ASOM 203.4 mg/dl and CSOM 511.5 mg/dl. The mean serum IgM levels were for controls 35 mg/dl, ASOM 64.1 mg/dl and CSOM 40 mg/dl; the MES levels were for ASOM 22.59 mg/dl and CSOM 3.44 mg/dl. The mean MES:serum ratios for IgG and IgM were between 0.1 and 0.4 in ASOM and CSOM. The ratio of serum IgG levels of controls to ASOM cases was 0.66 while that of controls to CSOM was 1.3. The corresponding ratios of IgM were 1.6 and 0.88. Multivariate analysis revealed a significant correlation between serum IgG levels of ASOM and CSOM (p = 0.043) and MES IgG (p = 0.02) in ASOM and CSOM but no correlation between serum IgG levels in controls and ASOM (p = 0.25), serum IgM levels in controls and CSOM (p = 0.62) and serum IgM levels in controls and ASOM (p = 0.73), ASOM and CSOM (p = 0.064) and MES IgM levels of ASOM and CSOM (p = 0.06). CONCLUSIONS: Monitoring of the serum and MES IgG in ASOM may provide a useful index to assess the possibility of progression to chronicity. This forms a database for the immunological status of SOM patients.


Subject(s)
Biomarkers/metabolism , Immunoglobulins/metabolism , Otitis Media, Suppurative/immunology , Acute Disease , Analysis of Variance , Biomarkers/analysis , Case-Control Studies , Child , Child, Preschool , Chronic Disease , Disease Progression , Ear, Middle/immunology , Enzyme-Linked Immunosorbent Assay , Female , Humans , Immunoglobulin G/analysis , Immunoglobulin G/metabolism , Immunoglobulin M/analysis , Immunoglobulin M/metabolism , Immunoglobulins/blood , Infant , Male , Monitoring, Physiologic , Otitis Media, Suppurative/diagnosis , Otitis Media, Suppurative/epidemiology , Probability , Prognosis , Reference Values , Risk Assessment , Sensitivity and Specificity , Severity of Illness Index
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