RPS19 and TYMS SNPs and Prevalent High Risk Human Papilloma Virus Infection in Nigerian Women

Famooto, Ayo; Al-Mujtaba, Maryam; Dareng, Eileen; Akarolo-Anthony, Sally; Ogbonna, Celestine C.; Offiong, Richard; Olaniyan, Olayinka; Wheeler, Cosette M.; Doumatey, Ayo P.; Rotimi, Charles N.; Adeyemo, Adebowale; Adebamowo, Clement

doi:10.1371/journal.pone.0066930

Cited by 20 publications

(33 citation statements)

References 23 publications

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“…However, the results from previous studies have been inconsistent (5–11). Several pathogens, particularly those capable of establishing persistent infections can affect cellular apoptotic pathways and potentially facilitate abnormal cell growth (12).…”

Section: Introductionmentioning

confidence: 90%

Mycoplasma hominis and Mycoplasma genitalium in the Vaginal Microbiota and Persistent High-Risk Human Papillomavirus Infection

Adebamowo

Zella

et al. 2017

Front. Public Health

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BackgroundRecent studies have suggested that the vaginal microenvironment plays a role in persistence of high-risk human papillomavirus (hrHPV) infection and thus cervical carcinogenesis. Furthermore, it has been shown that some mycoplasmas are efficient methylators and may facilitate carcinogenesis through methylation of hrHPV and cervical somatic cells. We examined associations between prevalence and persistence of Mycoplasma spp. in the vaginal microbiota, and prevalent as well as persistent hrHPV infections.MethodsWe examined 194 Nigerian women who were tested for hrHPV infection using SPF25/LiPA10 and we identified Mycoplasma genitalium and Mycoplasma hominis in their vaginal microbiota established by sequencing the V3–V4 hypervariable regions of the 16S rRNA gene. We defined the prevalence of M. genitalium, M. hominis, and hrHPV based on positive result of baseline tests, while persistence was defined as positive results from two consecutive tests. We used exact logistic regression models to estimate associations between Mycoplasma spp. and hrHPV infections.ResultsThe mean (SD) age of the study participants was 38 (8) years, 71% were HIV positive, 30% M. genitalium positive, 45% M. hominis positive, and 40% hrHPV positive at baseline. At follow-up, 16% of the women remained positive for M. genitalium, 30% for M. hominis, and 31% for hrHPV. There was a significant association between persistent M. hominis and persistent hrHPV (OR 8.78, 95% CI 1.49–51.6, p 0.01). Women who were positive for HIV and had persistent M. hominis had threefold increase in the odds of having persistent hrHPV infection (OR 3.28, 95% CI 1.31–8.74, p 0.008), compared to women who were negative for both.ConclusionWe found significant association between persistent M. hominis in the vaginal microbiota and persistent hrHPV in this study, but we could not rule out reverse causation. Our findings need to be replicated in larger, longitudinal studies and if confirmed, could have important diagnostic and therapeutic implications.

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Section: Introductionmentioning

confidence: 90%

Mycoplasma hominis and Mycoplasma genitalium in the Vaginal Microbiota and Persistent High-Risk Human Papillomavirus Infection

Adebamowo

Zella

et al. 2017

Front. Public Health

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“…In a subsequent study, the investigators examined 18,310 SNPs in 1,113 genes and reported that SNPs in PRDX3 and RPS19 were associated with HPV persistence and progression from persistent HPV infection to CIN3+ (10). We examined the association between the aforementioned SNPs and prevalent hrHPV infection in African women, and successfully replicated RPS19:rs2305809 and TYMS:rs2342700 (11).…”

Section: Introductionmentioning

confidence: 89%

“…We extracted DNA from the cervical exfoliated cells as previously described (11). Samples were tested for HPV DNA by hybridization of SPF 10 amplimers to a mixture of general HPV probes recognizing a broad range of high-risk, low-risk, and possible hrHPV genotypes in a microtiter plate format, as described previously (61).…”

Section: Hpv Detection By Spf 10 /Lipa 25mentioning

confidence: 99%

Genome-Wide Association Study of Prevalent and Persistent Cervical High-Risk Human Papillomavirus (HPV) Infection

Adeyemo

Rotimi

Olaniyan

et al. 2020

Preprint

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Background: Genetic factors may influence the susceptibility to high-risk human papillomavirus (hrHPV) infection and persistence. We conducted the first genome-wide association study (GWAS) to identify variants associated with cervical hrHPV infection and persistence.Methods: Participants were 517 Nigerian women evaluated at baseline and 6 months follow-up visits for HPV. HPV was characterized using SPF10/LiPA25. hrHPV infection was positive if at least one carcinogenic HPV genotype was detected in a sample provided at the baseline visit and persistent if at least one carcinogenic HPV genotype was detected in each of the samples provided at the baseline and follow-up visits. Genotyping was done using the Illumina Multi-Ethnic Genotyping Array (MEGA) and imputation was done using the African Genome Resources Haplotype Reference Panel. Association analysis was done for hrHPV infection (125 cases/392 controls) and for persistent hrHPV infection (51 cases/355 controls) under additive genetic models adjusted for age, HIV status and the first principal component (PC) of the genotypes.Results: The mean (±SD) age of the study participants was 38 (±8) years, 48% were HIV negative, 24% were hrHPV positive and 10% had persistent hrHPV infections. No single variant reached genome-wide significance (p < 5 X 10-8). The top three variants associated with hrHPV infections were intronic variants clustered in KLF12 (all OR: 7.06, p =1.43 x 10-6). The top variants associated with cervical hrHPV persistence were in DAP (OR: 6.86, p =7.15 x 10-8), NR5A2 (OR: 3.65, p =2.03 x 10-7) and MIR365-2 (OR: 7.71, p =2.63 x 10-7) gene regions. Conclusions: This exploratory GWAS yielded suggestive candidate risk loci for cervical hrHPV infection and persistence. The identified loci have biological annotation and functional data supporting their role in hrHPV infection and persistence. Given our limited sample size, larger discovery and replication studies are warranted to further characterize the reported associations.

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“…Evidence in LMICs suggests polymorphisms on the TYMS and RPS19 genes are associated with high-risk infection in Nigerian women, but overall in LMICs evidence is lacking on factors influencing effective HPV clearance ( 68 ). Several studies of women in HICs of African ancestry have identified that women of African-American descent despite having a similar prevalence of HPV, take longer to clear the virus ( 69 ).…”

Section: Molecular Diversity Affecting Communicable Causes Of Cancermentioning

confidence: 99%

“…So far, they have largely focussed on communicable disease such as trypanosomiasis, stroke and other neurological diseases affecting patients across the continent. Relevant to the field of oncology, some work has been undertaken into HPV infection in Nigeria ( 68 ), with the women included in this study demonstrating similar genetic susceptibility to infection as other populations. This group are set to expand into the field of breast cancer, which will provide useful data to study the genomic epidemiology of the disease on the African continent.…”

Section: Barriers To Global Research In Precision Medicinementioning

confidence: 99%

Global Inequities in Precision Medicine and Molecular Cancer Research

2018

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Precision medicine based upon molecular testing is heralded as a revolution in how cancer is prevented, diagnosed, and treated. Large efforts across the world aim to conduct comprehensive molecular profiling of disease to inform preclinical models, translational research studies and clinical trials. However, most studies have only been performed in patients from high-income countries. As the burden on non-communicable diseases increases, cancer will become a pressing burden across the world, disproportionately affecting low-middle income settings. There is emerging evidence that the molecular landscape of disease differs geographically and by genetic ancestry, which cannot be explained by environmental factors alone. There is a lack of good quality evidence that characterises the molecular landscape of cancers found in low-middle income countries. As cancer medicine becomes increasingly driven by molecular alterations in high-income settings, low-income settings may become left behind. Further efforts on an international scale must be made by researchers, funders, and policymakers to ensure cancer research addresses disease across the world, so models are not limited to subtypes of disease found in high-income countries. In this review, we discuss differences found in the molecular profiles of tumours worldwide and the implication this has for the future of global cancer care. Finally, we identify several barriers currently limiting progress in this field and innovative solutions, which may address these shortcomings.

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RPS19 and TYMS SNPs and Prevalent High Risk Human Papilloma Virus Infection in Nigerian Women

Cited by 20 publications

References 23 publications

Mycoplasma hominis and Mycoplasma genitalium in the Vaginal Microbiota and Persistent High-Risk Human Papillomavirus Infection

Mycoplasma hominis and Mycoplasma genitalium in the Vaginal Microbiota and Persistent High-Risk Human Papillomavirus Infection

Genome-Wide Association Study of Prevalent and Persistent Cervical High-Risk Human Papillomavirus (HPV) Infection

Global Inequities in Precision Medicine and Molecular Cancer Research

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