Polymorphisms in IL10 are associated with total Immunoglobulin e levels and Schistosoma mansoni infection intensity in a Brazilian population

A. V. Grant; M. I. Araujo; E. V. Ponte; R. R. Oliveira; A. A. Cruz; K. C. Barnes; T. H. Beaty

doi:10.1038/gene.2010.50

Polymorphisms in IL10 are associated with total Immunoglobulin e levels and Schistosoma mansoni infection intensity in a Brazilian population

A. V. Grant, M. I. Araujo, E. V. Ponte, R. R. Oliveira, A. A. Cruz, K. C. Barnes, T. H. Beaty

Bloomberg School of Public Health

Research output: Contribution to journal › Article › peer-review

22 Scopus citations

Abstract

Interleukin (IL)-10 is a regulatory cytokine of the helper T cell type 2 (TH2) pathway, which underlies both the host defense to helminthic infection and atopic diseases, including asthma. Although IL10 promoter polymorphisms are associated with increased atopy risk, IL10 variation has not been thoroughly explored in schistosomiasis-endemic populations. Three atopy-related IL10 promoter polymorphisms (rs1800896, rs1800871 and rs1800872), complemented by six tagging single-nucleotide polymorphisms (SNPs), were genotyped in 812 individuals in 318 nuclear families from a schistosomiasis-endemic area in Brazil. Associations between markers and total serum Immunoglobulin E (tIgE) levels, indicating non-specific activation of the TH2 pathway, and Schistosoma mansoni fecal egg counts, indicating burden of infection reflecting effectiveness of schistosomiasis host immunity, were performed using family-based transmission disequilibrium tests for quantitative traits (QTDTs). Alleles A, T and A at the three promoter SNPs rs1800896, rs1800871 and rs1800872 were associated with high tIgE levels in the same direction as in atopy populations (P=0.0008, 0.026 and 0.045), but not with egg counts. IL10 promoter polymorphisms appear to influence non-specific tIgE levels, but not schistosomiasis-specific immunity. The tagging SNP rs3024495 was associated with high S. mansoni egg counts (P=0.005), suggesting a novel locus in IL10 may influence clinically relevant burden of infection.

Original language	English (US)
Pages (from-to)	46-50
Number of pages	5
Journal	Genes and immunity
Volume	12
Issue number	1
DOIs	https://doi.org/10.1038/gene.2010.50
State	Published - Jan 2011

Keywords

IL-10
IgE
atopy
genetic susceptibility
promoter polymorphism
schistosomiasis

ASJC Scopus subject areas

Immunology
Genetics
Genetics(clinical)

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10.1038/gene.2010.50

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@article{64486a385e4943828376b6fa15f37582,

title = "Polymorphisms in IL10 are associated with total Immunoglobulin e levels and Schistosoma mansoni infection intensity in a Brazilian population",

abstract = "Interleukin (IL)-10 is a regulatory cytokine of the helper T cell type 2 (TH2) pathway, which underlies both the host defense to helminthic infection and atopic diseases, including asthma. Although IL10 promoter polymorphisms are associated with increased atopy risk, IL10 variation has not been thoroughly explored in schistosomiasis-endemic populations. Three atopy-related IL10 promoter polymorphisms (rs1800896, rs1800871 and rs1800872), complemented by six tagging single-nucleotide polymorphisms (SNPs), were genotyped in 812 individuals in 318 nuclear families from a schistosomiasis-endemic area in Brazil. Associations between markers and total serum Immunoglobulin E (tIgE) levels, indicating non-specific activation of the TH2 pathway, and Schistosoma mansoni fecal egg counts, indicating burden of infection reflecting effectiveness of schistosomiasis host immunity, were performed using family-based transmission disequilibrium tests for quantitative traits (QTDTs). Alleles A, T and A at the three promoter SNPs rs1800896, rs1800871 and rs1800872 were associated with high tIgE levels in the same direction as in atopy populations (P=0.0008, 0.026 and 0.045), but not with egg counts. IL10 promoter polymorphisms appear to influence non-specific tIgE levels, but not schistosomiasis-specific immunity. The tagging SNP rs3024495 was associated with high S. mansoni egg counts (P=0.005), suggesting a novel locus in IL10 may influence clinically relevant burden of infection.",

keywords = "IL-10, IgE, atopy, genetic susceptibility, promoter polymorphism, schistosomiasis",

author = "Grant, {A. V.} and Araujo, {M. I.} and Ponte, {E. V.} and Oliveira, {R. R.} and Cruz, {A. A.} and Barnes, {K. C.} and Beaty, {T. H.}",

note = "Funding Information: We thank the people of the endemic area in Conde from Buri, Camarao, Genipapo, Sempre Viva and Cobo for their participation in our study, the health liaisons, Adaliudes Conceic¸{\~a}o, Luciana Quintela, Ivanice Santos, the public health officers of the main Conde office, Anal{\'u} Lima, Benivaldo Valber Oliveira Silva and Iraci Santos Araujo and students from the Federal University of Bahia who assisted in data collection, Rafael Santana, Roberta Barbosa, Ana Paula Santana, Charlton Barros, Marcele Brad{\~a}o, Ludmila Almeida, Thiago Cardoso and Daniela Costa. We also thank Tracy Hand, Peisong Gao, Monica Campbell and Itael Evgey for conducting all of the genotyping experiments. Thanks to Dani Fallin and Alan Scott for helpful discussions, and to Priya Duggal and Sabine Plancoulaine for critical reading of the paper. This research was supported by Glaxo-Smith-Kline under the project WE445 entitled {\textquoteleft}Immunogenetics of Schistosomiasis and Asthma,{\textquoteright} and NIH grant # AI050024. KCB was supported in part by the Mary Beryl Patch Turnbull Scholar Program.",

year = "2011",

month = jan,

doi = "10.1038/gene.2010.50",

language = "English (US)",

volume = "12",

pages = "46--50",

journal = "Genes and Immunity",

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T1 - Polymorphisms in IL10 are associated with total Immunoglobulin e levels and Schistosoma mansoni infection intensity in a Brazilian population

AU - Grant, A. V.

AU - Araujo, M. I.

AU - Ponte, E. V.

AU - Oliveira, R. R.

AU - Cruz, A. A.

AU - Barnes, K. C.

AU - Beaty, T. H.

N1 - Funding Information: We thank the people of the endemic area in Conde from Buri, Camarao, Genipapo, Sempre Viva and Cobo for their participation in our study, the health liaisons, Adaliudes Conceic¸ão, Luciana Quintela, Ivanice Santos, the public health officers of the main Conde office, Analú Lima, Benivaldo Valber Oliveira Silva and Iraci Santos Araujo and students from the Federal University of Bahia who assisted in data collection, Rafael Santana, Roberta Barbosa, Ana Paula Santana, Charlton Barros, Marcele Bradão, Ludmila Almeida, Thiago Cardoso and Daniela Costa. We also thank Tracy Hand, Peisong Gao, Monica Campbell and Itael Evgey for conducting all of the genotyping experiments. Thanks to Dani Fallin and Alan Scott for helpful discussions, and to Priya Duggal and Sabine Plancoulaine for critical reading of the paper. This research was supported by Glaxo-Smith-Kline under the project WE445 entitled ‘Immunogenetics of Schistosomiasis and Asthma,’ and NIH grant # AI050024. KCB was supported in part by the Mary Beryl Patch Turnbull Scholar Program.

PY - 2011/1

Y1 - 2011/1

N2 - Interleukin (IL)-10 is a regulatory cytokine of the helper T cell type 2 (TH2) pathway, which underlies both the host defense to helminthic infection and atopic diseases, including asthma. Although IL10 promoter polymorphisms are associated with increased atopy risk, IL10 variation has not been thoroughly explored in schistosomiasis-endemic populations. Three atopy-related IL10 promoter polymorphisms (rs1800896, rs1800871 and rs1800872), complemented by six tagging single-nucleotide polymorphisms (SNPs), were genotyped in 812 individuals in 318 nuclear families from a schistosomiasis-endemic area in Brazil. Associations between markers and total serum Immunoglobulin E (tIgE) levels, indicating non-specific activation of the TH2 pathway, and Schistosoma mansoni fecal egg counts, indicating burden of infection reflecting effectiveness of schistosomiasis host immunity, were performed using family-based transmission disequilibrium tests for quantitative traits (QTDTs). Alleles A, T and A at the three promoter SNPs rs1800896, rs1800871 and rs1800872 were associated with high tIgE levels in the same direction as in atopy populations (P=0.0008, 0.026 and 0.045), but not with egg counts. IL10 promoter polymorphisms appear to influence non-specific tIgE levels, but not schistosomiasis-specific immunity. The tagging SNP rs3024495 was associated with high S. mansoni egg counts (P=0.005), suggesting a novel locus in IL10 may influence clinically relevant burden of infection.

AB - Interleukin (IL)-10 is a regulatory cytokine of the helper T cell type 2 (TH2) pathway, which underlies both the host defense to helminthic infection and atopic diseases, including asthma. Although IL10 promoter polymorphisms are associated with increased atopy risk, IL10 variation has not been thoroughly explored in schistosomiasis-endemic populations. Three atopy-related IL10 promoter polymorphisms (rs1800896, rs1800871 and rs1800872), complemented by six tagging single-nucleotide polymorphisms (SNPs), were genotyped in 812 individuals in 318 nuclear families from a schistosomiasis-endemic area in Brazil. Associations between markers and total serum Immunoglobulin E (tIgE) levels, indicating non-specific activation of the TH2 pathway, and Schistosoma mansoni fecal egg counts, indicating burden of infection reflecting effectiveness of schistosomiasis host immunity, were performed using family-based transmission disequilibrium tests for quantitative traits (QTDTs). Alleles A, T and A at the three promoter SNPs rs1800896, rs1800871 and rs1800872 were associated with high tIgE levels in the same direction as in atopy populations (P=0.0008, 0.026 and 0.045), but not with egg counts. IL10 promoter polymorphisms appear to influence non-specific tIgE levels, but not schistosomiasis-specific immunity. The tagging SNP rs3024495 was associated with high S. mansoni egg counts (P=0.005), suggesting a novel locus in IL10 may influence clinically relevant burden of infection.

KW - IL-10

KW - IgE

KW - atopy

KW - genetic susceptibility

KW - promoter polymorphism

KW - schistosomiasis

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DO - 10.1038/gene.2010.50

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JF - Genes and Immunity

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Polymorphisms in IL10 are associated with total Immunoglobulin e levels and Schistosoma mansoni infection intensity in a Brazilian population

Abstract

Keywords

ASJC Scopus subject areas

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