Interleukin-13 rs1800925/-1112C/T promoter single nucleotide polymorphism variant linked to anti-schistosomiasis in adult males in Murehwa District, Zimbabwe

Choto, Emilia; Mduluza, Takafira; Chimbari, Moses John

doi:10.1371/journal.pone.0252220

Cited by 5 publications

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“…Diverse findings have been reported by different research groups studying the SNV rs1800925 in the promoter region (−1112 C/T) and its association with IL-13 levels. One study observed an association between high levels of IL-13 and the CC genotypes in schistosomiasis-uninfected individuals in Zimbabwe ( 60 ), while another study indicated that TT genotypes are correlated with high IL-13 levels in S. japonicum -infected individuals ( 61 ). Another SNV rs2069739A>G, an intron variant of IL13, has also been linked with plasma levels of IL-13.…”

Section: Discussionmentioning

confidence: 99%

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A fine mapping of single nucleotide variants and haplotype analysis of IL13 gene in patients with Leishmania guyanensis-cutaneous leishmaniasis and plasma cytokines IL-4, IL-5, and IL-13

Junior,

Souza,

Silva

et al. 2023

Front. Immunol.

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IntroductionLeishmaniasis 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.MethodsWe 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). ResultsOur 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. ConclusionsOverall, 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.

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Section: Discussionmentioning

confidence: 99%

“…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 ).…”

Section: Discussionmentioning

confidence: 99%

A fine mapping of single nucleotide variants and haplotype analysis of IL13 gene in patients with Leishmania guyanensis-cutaneous leishmaniasis and plasma cytokines IL-4, IL-5, and IL-13

Junior,

Souza,

Silva

et al. 2023

Front. Immunol.

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“…Genetic studies have revealed associations between SNPs in genes encoding cytokines and TFs and susceptibility to schistosomiasis, including in STAT6 , IL4 , IL5 , IL10 , and IL13 [ 15 – 21 ]. Recently, Choto and colleagues identified an association between IL13 rs1800925 and elevated IL-13 concentrations in schistosome-uninfected but not schistosome-infected individuals in Zimbabwe [ 22 ]. In addition, Marume and colleagues identified an association between IL10 SNP rs1800871, protection from S .…”

Section: Introductionmentioning

confidence: 99%

Frequency distribution of cytokine and associated transcription factor single nucleotide polymorphisms in Zimbabweans: Impact on schistosome infection and cytokine levels

et al. 2022

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Cytokines mediate T-helper (TH) 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 TH2-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 TH1- and TH2-associated genes highlights the role of both in regulating and controlling responses to Schistosoma.

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Association between polymorphisms of IL4, IL13, IL10, STAT6 and IFNG genes, cytokines and immunoglobulin E levels with high burden of Schistosoma mansoni in children from schistosomiasis endemic areas of Cameroon

Mewamba

Noyes

Tiofack

et al. 2023

Infection, Genetics and Evolution

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Interleukin-13 rs1800925/-1112C/T promoter single nucleotide polymorphism variant linked to anti-schistosomiasis in adult males in Murehwa District, Zimbabwe

Cited by 5 publications

References 63 publications

A fine mapping of single nucleotide variants and haplotype analysis of IL13 gene in patients with Leishmania guyanensis-cutaneous leishmaniasis and plasma cytokines IL-4, IL-5, and IL-13

A fine mapping of single nucleotide variants and haplotype analysis of IL13 gene in patients with Leishmania guyanensis-cutaneous leishmaniasis and plasma cytokines IL-4, IL-5, and IL-13

Frequency distribution of cytokine and associated transcription factor single nucleotide polymorphisms in Zimbabweans: Impact on schistosome infection and cytokine levels

Association between polymorphisms of IL4, IL13, IL10, STAT6 and IFNG genes, cytokines and immunoglobulin E levels with high burden of Schistosoma mansoni in children from schistosomiasis endemic areas of Cameroon

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