An asthma-associated genetic variant of STAT6 predicts low burden of ascaris worm infestation

Peisong, Gao; Mao, Xiao-Quan; Enomoto, Tadao; Feng, Zijian; Gloria‐Bottini, F.; Bottini, E; Shirakawa, Taro; Sun, Dejan; Hopkin, Julian M.

doi:10.1038/sj.gene.6364030

Cited by 70 publications

(59 citation statements)

References 35 publications

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“…Our findings are thus consistent with prior studies showing the strong role of the SM1 locus in S. mansoni infection levels, 2 the association of rs1800925 to high S. haematobium infection levels in an independent study in Kenya, 13 and the association of STAT6 polymorphisms to infection levels in other helminth infections. 21 No association was found for the other SNPs that are in linkage disequilibrium with rs1800925. Among these markers, we first noticed polymorphism rs2040704 (located in the 3 0 untranslated region of RAD50).…”

Section: Discussionmentioning

confidence: 96%

Association of rs7719175, located in the IL13 gene promoter, with Schistosoma haematobium infection levels and identification of a susceptibility haplotype

et al. 2010

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Urinary schistosomiasis is a parasitic disease caused by Schistosoma haematobium helminths. S. haematobium eggs may remain trapped within the bladder or the ureter walls, causing major pathological disorders in the urogenital system. The polymorphism rs1800925(C/T) of the IL13 gene promoter, which is functional, has previously been associated with susceptibility to S. haematobium infection. The aim of this study was to further our understanding and to determine whether, in the 5q31-q33 region, rs1800925 affects infection levels alone or in synergy with other polymorphisms. After sequencing the IL13 promoter and increasing the single-nucleotide polymorphism density, we performed a linkage disequilibrium analysis between rs1800925 and the other markers in a Malian population. Multivariate linear regression analysis and electrophoretic mobility shift assay (EMSA) were performed to characterized markers in linkage disequilibrium with rs1800925. An additional polymorphism, rs7719175, in the IL13 promoter was associated with controlling infection levels in multivariate analysis. The haplotype rs7719175T-rs1800925C was associated with high infection levels. EMSA indicated that rs7719175 affects the binding of transcriptional factors to the promoter region. Polymorphisms rs7719175 and rs1800925 have a synergistic role in the control of infection levels caused by S. haematobium and using them as a haplotype allows a better discrimination between infected subjects.

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Section: Discussionmentioning

confidence: 96%

Association of rs7719175, located in the IL13 gene promoter, with Schistosoma haematobium infection levels and identification of a susceptibility haplotype

et al. 2010

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“…A major association was inferred between a genetic variant (G/A 4219) of the 3'-UTR regulatory element of the STAT6 gene in an Ascaris infection study (Peisong et al 2004). The study explicitly concluded that the homozygous state of this genetic variant indicated a strong association with diminished Ascaris burden in children living in an area of endemic infection.…”

Section: Discussionmentioning

confidence: 86%

“…In particular, one promoter polymorphism (rs324013) in STAT6 was found to be associated with the control of infection levels (He et al 2008). Similarly, a STAT6 variant (rs324015) was associated with resistance to Ascaris in children from an endemic area in China (Peisong et al 2004). A very recent study in the context of active inflammation in asthma patients (Pillemer et al 2009) concluded that blocking the dominant stimulatory effects of IL4 and IL13 via STAT6 on disease-associated Th2 cells is expected to result in a beneficial effect in asthma patients.…”

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confidence: 99%

Molecular characterization of regulatory polymorphisms in the promoter region of the STAT6 gene in a Gabonese population

Velavan

Bechlars

Tomiuk

et al. 2011

Mem. Inst. Oswaldo Cruz

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Parasites remain competent invaders of host immunity. Their invasion strategies have proven to impact immunorelevant genes leading to diversity among gene families. We focussed on signal transducer and activator of transcription (STAT6) factor that plays a fundamental role in signal transduction and activation of transcription. Recent studies have highlighted the role of STAT6 variants in control of infection levels. We identified and investigated regulatory single nucleotide polymorphisms (SNPs) in the promoter regions of the STAT6 gene in a group of Gabonese individuals exposed to a variety of parasitic infections. Three promoter variants were identified in 40 individual subjects. We further validated these promoter variants for their allelic gene expression using transient transfection assays. One promoter variant, rs3024944 (G/C), revealed an altered expression of the marker gene. The identification of function-altering SNPs in the promoter may facilitate studying parasite susceptibility in association studies

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“…Associational studies conducted in the past have demonstrated the HLA 30/31, STAT 6 and β 2 -adrenoreceptor genes all play a role in susceptibility to Ascaris infection in humans (Holland et al 1992;Ramsay et al 1999;Peisong et al 2004), highlighting the multigenic mechanism of resistance. Furthermore, a recent candidate gene study, undertaken in an Ascaris-endemic Columbian population cited 2 genes as being key to resistance to Ascaris infection, one of which is located in one of the QTL detected in the Jirel pedigree population (Williams-Blangero et al 2002Acevedo et al 2009).…”

Section: Introductionmentioning

confidence: 99%

The role of Intelectin-2 in resistance toAscaris suumlung larval burdens in susceptible and resistant mouse strains

et al. 2011

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SUMMARYThe underlying mechanism of predisposition toAscarisinfection is not yet understood but host genetics are thought to play a fundamental role. We investigated the association between the Intelectin-2 gene and resistance in F2mice derived from mouse strains known to be susceptible and resistant to infection.Ascarislarvae were isolated from murine lungs and the number of copies of the Intelectin-2 gene was determined in F2mice. Intelectin-2 gene copy number was not significantly linked to larval burden. In a pilot experiment, the response to infection in parental mice of both sexes was observed in order to address the suitablity of female F2mice. No overall significant sex effect was detected. However, a divergence in resistance/susceptibility status was observed between male and, female hybrid offspring. The responsiveness toAscarisin mice is likely to be controlled by multiple genes and, despite a unique absence from the susceptible C57BL/6j strain, the Intelectin-2 gene does not play a significant role in resistance. The observed intra-strain variation in larval burden requires further investigation but we hypothesize that it stems from social/dominance hierarchies created by the presence of female mice and possibly subsequent hormonal perturbations that modify the intensity of the immune response.

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An asthma-associated genetic variant of STAT6 predicts low burden of ascaris worm infestation

Cited by 70 publications

References 35 publications

Association of rs7719175, located in the IL13 gene promoter, with Schistosoma haematobium infection levels and identification of a susceptibility haplotype

Association of rs7719175, located in the IL13 gene promoter, with Schistosoma haematobium infection levels and identification of a susceptibility haplotype

Molecular characterization of regulatory polymorphisms in the promoter region of the STAT6 gene in a Gabonese population

The role of Intelectin-2 in resistance toAscaris suumlung larval burdens in susceptible and resistant mouse strains

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