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Genetic factors influencing Immunogl...

Grant, Audrey V.

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Genetic factors influencing Immunoglobulin E levels and burden of Schistosoma mansoni infection in an endemic population in Brazil.

Record Type:	Language materials, printed : Monograph/item
Title/Author:	Genetic factors influencing Immunoglobulin E levels and burden of Schistosoma mansoni infection in an endemic population in Brazil./
Author:	Grant, Audrey V.
Description:	259 p.
Notes:	Adviser: Terri H. Beaty.
Contained By:	Dissertation Abstracts International68-11B.
Subject:	Biology, Genetics. -
Online resource:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3288463
ISBN:	9780549313397

Genetic factors influencing Immunoglobulin E levels and burden of Schistosoma mansoni infection in an endemic population in Brazil.
Grant, Audrey V.

Genetic factors influencing Immunoglobulin E levels and burden of Schistosoma mansoni infection in an endemic population in Brazil. - 259 p.

Adviser: Terri H. Beaty.

Thesis (Ph.D.)--The Johns Hopkins University, 2008.

The genetic basis for total Immunoglobulin E (tIgE) levels has been established in industrialized study populations, but not in populations endemic for helminths. Both environmental allergens and helminthic infection stimulate the TH2 immune pathway, leading to IgE production. Variants in the genes for TH2 cytokines IL-4, IL-13 and IL-5, and the regulatory cytokine IL-10, may influence tIgE levels, specific IgE (spIgE) levels to a panel of common allergens and schistosomiasis worm burden as measured by count of Schistosoma mansoni eggs per gram of fecal matter in a population endemic for S. mansoni.

ISBN: 9780549313397Subjects--Topical Terms:

1017730
Biology, Genetics.

Genetic factors influencing Immunoglobulin E levels and burden of Schistosoma mansoni infection in an endemic population in Brazil.
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020 $a 9780549313397
035 $a (UMI)AAI3288463
035 $a AAI3288463
040 $a UMI $c UMI
100 1 $a Grant, Audrey V. $3 1263083
245 1 0 $a Genetic factors influencing Immunoglobulin E levels and burden of Schistosoma mansoni infection in an endemic population in Brazil.
300 $a 259 p.
500 $a Adviser: Terri H. Beaty.
500 $a Source: Dissertation Abstracts International, Volume: 68-11, Section: B, page: 7223.
502 $a Thesis (Ph.D.)--The Johns Hopkins University, 2008.
520 $a The genetic basis for total Immunoglobulin E (tIgE) levels has been established in industrialized study populations, but not in populations endemic for helminths. Both environmental allergens and helminthic infection stimulate the TH2 immune pathway, leading to IgE production. Variants in the genes for TH2 cytokines IL-4, IL-13 and IL-5, and the regulatory cytokine IL-10, may influence tIgE levels, specific IgE (spIgE) levels to a panel of common allergens and schistosomiasis worm burden as measured by count of Schistosoma mansoni eggs per gram of fecal matter in a population endemic for S. mansoni.
520 $a In this dissertation, the first paper examines the distributions of the three phenotypes: tIgE levels, spIgE levels, and S. mansoni egg count using familial relationships connecting individuals in the study population of 822 subjects of African descent from Conde, Brazil. We obtained estimates of heritability at 60% for tIgE levels, 48% for spIgE levels and 31 % for S. mansoni egg count after log-transforming trait values and adjusting them for individual-level covariates under an additive polygenic model.
520 $a In the second paper, results for tests for associations are reported between 33 tagging single nucleotide polymorphisms (SNPs) in the four candidate genes and the three quantitative traits and risk of lifetime "wheeze," a hallmark asthma symptom, using ANOVA and family-based association tests. Among IL10 promoter polymorphisms, allele "A" of marker rs 1800896 was found to be most strongly associated with high tIgE levels. A novel region at the 3' end of IL10 was found to be linked and associated with S. mansoni egg count. In IL13, a 2-SNP window including a well-known non-synonymous coding variant showed evidence for linkage and association with wheeze, and this same variant was also found to be protective against high S. mansoni egg count. For IL4, alleles at all tagging SNPs were found to be associated with elevated tIgE levels among independent subjects 15 years or older, but not among younger children.
520 $a Findings were strongest for tIgE levels, with high heritability and highly statistically significant associations with genetic variants, particularly for IL10 and IL4 promoter polymorphisms. Genetic associations were in the same direction as published findings in atopic populations. There was some evidence supporting the hypothesis that selective pressures may have resulted in protective genetic variants against high levels of helminhtic infection, that also predispose to atopic disease. While association results presented here account for some of the heritability found for tIgE levels, other TH2 pathway genes require further investigation, and further research at other loci is needed to determine genetic factors influencing intensity of S. masoni intensity of infection.
590 $a School code: 0098.
650 4 $a Biology, Genetics. $3 1017730
650 4 $a Biology, Parasitology. $3 1028974
650 4 $a Health Sciences, Epidemiology. $3 1019544
650 4 $a Health Sciences, Immunology. $3 1017716
690 $a 0369
690 $a 0718
690 $a 0766
690 $a 0982
710 2 $a The Johns Hopkins University. $3 1017431
773 0 $t Dissertation Abstracts International $g 68-11B.
790 $a 0098
790 1 0 $a Beaty, Terri H., $e advisor
791 $a Ph.D.
792 $a 2008
856 4 0 $u http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3288463