A cluster of seven tightly linked polymorphisms in the IL-13 gene is associated with total serum IgE levels in three populations of white children

Graves, Penelope E.; Kabesch, Michael; Halonen, Marilyn; Holberg, Catharine J.; Baldini, Mauro; Fritzsch, Christian; Weiland, Stephan K.; Erickson, Robert P.; Mutius, Erika von; Martínez, Fernando D.

doi:10.1067/mai.2000.104940

Cited by 382 publications

(317 citation statements)

References 42 publications

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“…21 Furthermore, no significant ethnic or genetic differences exist between children from both parts of Germany, as shown previously. 11,22 In this study all associations have been tested separately in both populations to ensure that the effects of the respective polymorphisms would be reproducible. The separate analysis in both populations is provided in the supplementary Tables E3a, E3b, E4a, and E4b.…”

Section: Discussionmentioning

confidence: 99%

“…10 Recently, we have reported a highly significant association of total serum IgE levels with a cluster of 7 tightly linked polymorphisms in the IL13 gene in 3 independent populations. 11 However, because the IL4 gene is located just 10 kb centromeric of the IL13 gene, it could be argued that the associations observed with the polymorphisms in IL13 are due to linkage disequilibrium with polymorphisms in the IL4 gene apart from those known thus far.…”

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confidence: 99%

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A complete screening of the IL4 gene

Kabesch¹,

Tzotcheva²,

Carr³

et al. 2003

Journal of Allergy and Clinical Immunology

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106

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

A complete screening of the IL4 gene

Kabesch¹,

Tzotcheva²,

Carr³

et al. 2003

Journal of Allergy and Clinical Immunology

Self Cite

106

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“…4 The IL13 gene encompasses 2938 bp and includes four exons, 56 bp of 5 0 UTR and 828 bp of 3 0 UTR ( Figure 1). Previous studies [6][7][8][9][10][11] and single-nucleotide polymorphism (SNP) discovery initiatives such as the University of Washington-Fred Hutchinson Cancer Research Center Variation Discovery Resource (http://pga.gs.washington.edu/) and SNP500Cancer (http://snp500cancer.nci.-nih.gov/) have identified 32 SNPs in the IL13 gene and its promoter region in European, European-American, Chinese, Japanese, African American and African samples. These include two SNPs in the promoter region and a single nonsynonymous substitution (2043G4A, Arg130Gln), located in exon 4.…”

Section: Introductionmentioning

confidence: 99%

“…These include two SNPs in the promoter region and a single nonsynonymous substitution (2043G4A, Arg130Gln), located in exon 4. Epidemiological studies in different populations have shown an association of the À1111T allele in the promoter region, 8,9,12 or of the Gln130 allele, 6,7,12 with different asthma-related disorders and proximal risk phenotypes, such as serum IL-13 and IgE levels. Moreover, Hoerauf et al 13 have identified an association between the Gln130 allele and sowda, an immunological hyper-reactive form of onchocerciasis.…”

Section: Introductionmentioning

confidence: 99%

Divergent patterns of linkage disequilibrium and haplotype structure across global populations at the interleukin-13 (IL13) locus

Tarazona‐Santos

Tishkoff

2004

Genes Immun

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Interleukin-13 (IL-13) is a cytokine involved in Th2 immune response, which plays a role in susceptibility to infection by extracellular parasites as well as complex diseases of the immune system such as asthma and allergies. To determine the pattern of genetic diversity at the IL13 gene, we sequenced 3950 bp encompassing the IL13 gene and its promoter in 264 chromosomes from individuals originating from East and West Africa, Europe, China and South America. Thirty-one singlenucleotide polymorphisms (SNPs) arranged in 88 haplotypes were indentified, including the nonsynonymous substitution Arg130Gln in exon 4, which differs in frequency across ethnic groups. We show that genetic diversity and linkage disequilibrium (LD) are not evenly distributed across the gene and that sites in the 5 0 and 3 0 regions of the gene show strong differentiation among continental groups. We observe a divergent pattern of haplotype variation and LD across geographic regions and we identify a set of htSNPs that will be useful for functional genetic association studies of complex disease. We use several statistical tests to distinguish the effects of natural selection and demographic history on patterns of genetic diversity at the IL13 locus.

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“…5,6 Genome-wide linkage studies have identified evidence of linkage of this region with bronchial asthma [7][8][9] and other inflammatory disease such as Crohn's disease. 10 Despite numerous genetic-association studies, [11][12][13][14][15][16][17] the involvement of the IL-13/ IL-4 locus in susceptibility to allergic disease is unclear. Since the two loci are so closely linked and similar in function, it is not clear as to which might be responsible for the observed association.…”

Section: Introductionmentioning

confidence: 99%

Local adaptation and population differentiation at the interleukin 13 and interleukin 4 loci

et al. 2004

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A 25.6 kb region at chromosome 5q31, covering the entire human interleukin 13 (IL-13) and interleukin 4 (IL-4) genes, has been reported to be associated with bronchial asthma. We have examined nucleotide variations at this locus in African, European American, and Japanese populations, using 120 diallelic variants. A block of strong linkage disequilibrium (LD) (|D 0 |40.7) spans a 10 kb region containing IL-4 in European American and Japanese populations, and is present but less clear in African samples. Two major haplotypes at IL-4 account for 480% of haplotypes in European Americans and Japanese. These haplotypes are common and quite diverged from each other and the ancestral haplotype, resulting in highly significant deviations from neutrality. F ST statistics show that European American and Japanese populations are unusually distinct at the IL-4 locus. The most common haplotype in the European American population is much less common in the Japanese population, and vice versa. This implies that natural selection has acted on IL-4 haplotypes differently in different populations. This selected variation at IL-4 may account for some genetic variance underlying susceptibility to asthma and other allergic diseases. The strong LD observed in the IL-4 region may allow more efficient disease-association studies using this locus.

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A cluster of seven tightly linked polymorphisms in the IL-13 gene is associated with total serum IgE levels in three populations of white children

Cited by 382 publications

References 42 publications

A complete screening of the IL4 gene

A complete screening of the IL4 gene

Divergent patterns of linkage disequilibrium and haplotype structure across global populations at the interleukin-13 (IL13) locus

Local adaptation and population differentiation at the interleukin 13 and interleukin 4 loci

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