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Background
Chronic schistosomiasis is predominantly induced through up-regulation of inflammatory cytokines such as interleukin (IL)-13. IL-13 may contribute to the disease outcomes by increasing eosinophil infiltration thereby promoting fibrosis. IL-13 may act as an immunosuppressive inflammatory cytokine that may promote carcinogenesis and also m...
Context in source publication
Context 1
... prevalence was 13.7% (n = 50) with S. haematobium infections prevalence of 12.3% (n = 45) and S. mansoni infection prevalence of 1.4% (n = 5). Majority of the infected participants were young adults and they harboured mostly light infections as shown in the participants demographic Table 1. The overall schistosomiasis for both S. haematobium and S. mansoni prevalence in each village was as follows: Dombwe 3.2%, Mutize 0%, Jekwa 3.5%, Guzha 10%, Magaya 13.2%, Inyagui 11.9%, Kapasura 37.7% and Kareza 13.5%. ...Citations
... Another SNV rs2069739A>G, an intron variant of IL13, has also been linked with plasma levels of IL-13. Carriers of the allele A of SNV rs2069739 are associated with an increased risk of having low plasma concentrations of IL-13 (30,60). ...
Introduction
Leishmaniasis continues to pose a substantial health burden in 97 countries worldwide. The progression and outcome of Leishmania infection are influenced by various factors, including the cytokine milieu, the skin microbiota at the infection site, the specific Leishmania species involved, the genetic background of the host, and the parasite load. In endemic regions to leishmaniasis, only a fraction of individuals infected actually develops the disease. Overexpression of IL-13 in naturally resistant C57BL/6 mice renders them susceptible to L. major infection. Haplotypes constructed from several single nucleotide variant (SNV) along a chromosome fragment may provide insight into any SNV near the fragment that may be genuinely associated with a phenotype in genetic association studies.
Methods
We investigated nine SNVs (SNV1rs1881457A>C, SNV2rs1295687C>G, SNV3rs2069744C>T, SNV4rs2069747C>T, SNV5rs20541A>G, SNV6rs1295685A>G, SNV7rs848A>C, SNV8rs2069750G >C, and SNV9rs847T>C) spanning the entire IL13 gene in patients with L. guyanensis cutaneous leishmaniasis (Lg-CL).
Results
Our analysis did not reveal any significant association between the SNVs and susceptibility/protection against Lg-CL development. However, haplotype analysis, excluding SNV4rs2069747 and SNV8rs2069750 due to low minor allele frequency, revealed that carriers of the haplotype CCCTAAC had a 93% reduced likelihood developing Lg-CL. Similarly, the haplotypes ACCCGCT (ORadj=0.02 [95% CI 0.00–0.07]; p-value, 6.0×10⁻¹⁹) and AGCTAAC (ORadj=0.00[95% CI 0.00–0.00]; p-value 2.7×10⁻¹²) appeared to provide protection against the development of Lg-CL. Conversely, carriers of haplotype ACCTGCC have 190% increased likelihood of developing Lg-CL (ORadj=2.9 [95%CI 1.68–5.2]; p-value, 2.5×10⁻⁶). Similarly, haplotype ACCCAAT (ORadj=2.7 [95%CI 1.5–4.7]; p-value, 3.2×10⁻⁵) and haplotype AGCCGCC are associated with susceptibility to the development of Lg-CL (ORadj=1.7[95%CI 1.04–2.8]; p-value, 0.01). In our investigation, we also found a correlation between the genotypes of rs2069744, rs20541, rs1295685, rs847, and rs848 and plasma IL-5 levels among Lg-Cl patients. Furthermore, rs20541 showed a correlation with plasma IL-13 levels among Lg-Cl patients, while rs2069744 and rs848 showed a correlation with plasma IL-4 levels among the same group.
Conclusions
Overall, our study identifies three haplotypes of IL13 associated with resistance to disease development and three haplotypes linked to susceptibility. These findings suggest the possibility of a variant outside the gene region that may contribute, in conjunction with other genes, to differences in susceptibility and partially to the pathology.
... The largest study for cervical cancer cohorts in Zimbabwe has mostly focused on the relationship with HIV and other reproductive infections [23]. Furthermore, there are also studies that have attempted to elucidate the association of genetic polymorphisms with cancer susceptibility in Zimbabwe [24][25][26][27][28], but these datasets may not have been established using harmonised methods, which can limit genomic applications. ...
Background
Research infrastructures such as biorepositories are essential to facilitate genomics and its growing applications in health research and translational medicine in Africa. Using a cervical cancer cohort, this study describes the establishment of a biorepository consisting of biospecimens and matched phenotype data for use in genomic association analysis and pharmacogenomics research.
Method
Women aged > 18 years with a recent histologically confirmed cervical cancer diagnosis were recruited. A workflow pipeline was developed to collect, store, and analyse biospecimens comprising donor recruitment and informed consent, followed by data and biospecimen collection, nucleic acid extraction, storage of genomic DNA, genetic characterization, data integration, data analysis and data interpretation. The biospecimen and data storage infrastructure included shared -20 °C to -80 °C freezers, lockable cupboards, secured access-controlled laptop, password protected online data storage on OneDrive software. The biospecimen or data storage, transfer and sharing were compliant with the local and international biospecimen and data protection laws and policies, to ensure donor privacy, trust, and benefits for the wider community.
Results
This initial establishment of the biorepository recruited 410 women with cervical cancer. The mean (± SD) age of the donors was 52 (± 12) years, comprising stage I (15%), stage II (44%), stage III (47%) and stage IV (6%) disease. The biorepository includes whole blood and corresponding genomic DNA from 311 (75.9%) donors, and tumour biospecimens and corresponding tumour DNA from 258 (62.9%) donors. Datasets included information on sociodemographic characteristics, lifestyle, family history, clinical information, and HPV genotype. Treatment response was followed up for 12 months, namely, treatment-induced toxicities, survival vs. mortality, and disease status, that is disease-free survival, progression or relapse, 12 months after therapy commencement.
Conclusion
The current work highlights a framework for developing a cancer genomics cohort-based biorepository on a limited budget. Such a resource plays a central role in advancing genomics research towards the implementation of personalised management of cancer.
Living conditions in the Arctic zone are extremely unfavorable for living and contribute to the development of a number of diseases due to suppression of the functions of the immune system. Cytokines are one of the main mediators of the immune system; they are encoded by genes with a high degree of polymorphism. This study examined the distribution of genetic variants in the cytokine genes (rs2243250 IL4, rs1800925 IL13) among the Nenets, Dolgan-Nganasan and Slavs. It was previously established that these mutations are associated with the level of expression of these interleukins and their production, which leads to changes in the impairment of the immune response to the influence of the pathogen. The study showed the predominance of genotypes CT and TT of the rs2243250 IL4 polymorphism, and genotype CC of the rs1800925 IL13 polymorphism in the Nenets and Dolgan-Nganasan populations. The results obtained suggest that the indigenous inhabitants of the Russian Arctic have a genetically determined rapid immune response and protection against the development of allergic diseases compared to the Slavs.
Eliminating schistosomiasis as a public health problem by 2030 requires a better understanding of the disease transmission, especially the asymmetric distribution of worm burden in individuals living and sharing the same environment. It is in this light that this study was designed to identify human genetic determinants associated with high burden of S. mansoni and also with the plasma concentrations of IgE and four cytokines in children from two schistosomiasis endemic areas of Cameroon. In school-aged children of schistosomiasis endemic areas of Makenene and Nom-Kandi of Cameroon, S. mansoni infections and their infection intensities were evaluated in urine and stool samples using respectively the Point-of-care Circulating Cathodic Antigen test (POC-CCA) and the Kato Katz (KK) test. Thereafter, blood samples were collected in children harbouring high burden of schistosome infections as well as in their parents and siblings. DNA extracts and plasma were obtained from blood. Polymorphisms at 14 loci of five genes were assessed using PCR-restriction fragment length polymorphism and amplification-refractory mutation system. The ELISA test enabled to determine the plasma concentrations of IgE, IL-13, IL-10, IL-4 and IFN-γ. The prevalence of S. mansoni infections was significantly higher (P < 0.0001 for POC-CCA; P = 0.001 for KK) in Makenene (48.6% for POC-CCA and 7.9% for KK) compared to Nom-Kandi (31% for POC-CCA and 4.3% for KK). The infection intensities were also higher (P < 0.0001 for POC-CCA; P = 0.001 for KK) in children from Makenene than those from Nom-Kandi. The allele C of SNP rs3024974 of STAT6 was associated with an increased risk of bearing high burden of S. mansoni both in the additive (p = 0.009) and recessive model (p = 0.01) while the allele C of SNP rs1800871 of IL10 was protective (p = 0.0009) against high burden of S. mansoni. The alleles A of SNP rs2069739 of IL13 and G of SNP rs2243283 of IL4 were associated with an increased risk of having low plasma concentrations of IL-13 (P = 0.04) and IL-10 (P = 0.04), respectively. This study showed that host genetic polymorphisms may influence the outcome (high or low worm burden) of S. mansoni infections and also the plasma concentrations of some cytokines.
Cytokines mediate T-helper (T H ) responses that are crucial for determining the course of infection and disease. The expression of cytokines is regulated by transcription factors (TFs). Here we present the frequencies of single nucleotide polymorphisms (SNPs) in cytokine and TF genes in a Zimbabwean population, and further relate SNPs to susceptibility to schistosomiasis and cytokine levels. Individuals (N = 850) were genotyped for SNPs across the cytokines IL4 , IL10 , IL13 , IL33 , and IFNG , and their TFs STAT4 , STAT5A/B , STAT6 , GATA3 , FOXP3 , and TBX21 to determine allele frequencies. Circulatory levels of systemic and parasite-specific IL-4, IL-5, IL-10, IL-13, and IFNγ were quantified via enzyme-linked immunosorbent assay. Schistosoma haematobium infection was determined by enumerating parasite eggs excreted in urine by microscopy. SNP allele frequencies were related to infection status by case-control analysis and logistic regression, and egg burdens and systemic and parasite-specific cytokine levels by analysis of variance and linear regression. Novel findings were i) IL4 rs2070874*T’s association with protection from schistosomiasis, as carriage of ≥1 allele gave an odds ratio of infection of 0.597 (95% CIs, 0.421–0.848, p = 0.0021) and IFNG rs2069727*G’s association with susceptibility to schistosomiasis as carriage of ≥1 allele gave an odds ratio of infection of 1.692 (1.229–2.33, p = 0.0013). Neither IL4 rs2070874*T nor IFNG rs2069727*G were significantly associated with cytokine levels. This study found T H 2-upregulating SNPs were more frequent among the Zimbabwean sample compared to African and European populations, highlighting the value of immunogenetic studies of African populations in the context of infectious diseases and other conditions, including allergic and atopic disease. In addition, the identification of novel infection-associated alleles in both T H 1- and T H 2-associated genes highlights the role of both in regulating and controlling responses to Schistosoma .
