Evidence for a Locus Regulating Total Serum IgE Levels Mapping to Chromosome 5

Meyers, Deborah A.; Postma, Dirkje S.; Panhuysen, Carolien; Xu, Jianfeng; Amelung, Pamela J.; Levitt, Roy C.; Bleecker, ER

doi:10.1006/geno.1994.1524

Cited by 374 publications

(224 citation statements)

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“…Chromosome 5q31-q33 is linked to atopy and/or asthma and bronchial hyper-responsiveness. 8,[22][23][24][25][26][27][28] Thus, the weak but positive findings of linkage to 5q33 in the present study may reflect one of the loci common to asthma and SAR.…”

Section: Discussionmentioning

confidence: 48%

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A genome-wide linkage analysis of orchard grass-sensitive childhood seasonal allergic rhinitis in Japanese families

et al. 2002

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Section: Discussionmentioning

confidence: 48%

“…Linkage of atopy and total serum IgE levels to chromosome 5q31-q33 and 12q24 has been reported. 8,[22][23][24][25][26][27][28][29] Weak linkage of asthma to chromosome 3p24 was also reported in the Hutterites. 6 Suggestive evidence for linkage of specific IgE against OG to 4p16.1, 11q14.3, and 16p12.3 was observed in the present study.…”

Section: Discussionmentioning

confidence: 80%

A genome-wide linkage analysis of orchard grass-sensitive childhood seasonal allergic rhinitis in Japanese families

et al. 2002

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“…1,2 Recently, the 5q31-33 region was reported to be linked to Plasmodium falciparum blood infection levels in Burkina Faso. 3 Moreover, this region is known to show linkage to plasma immunoglobulin E (IgE) levels 4,5 and schistosomiasis infection. 6,7 It is therefore interesting to analyze genes in this region for detecting variants associated with susceptibility or resistance to severe malaria.…”

Section: Introductionmentioning

confidence: 99%

A single-nucleotide substitution from C to T at position −1055 in the IL-13 promoter is associated with protection from severe malaria in Thailand

et al. 2003

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We examined a possible association of single-nucleotide polymorphisms (SNPs) in the promoters of IL-3, IL-4, and IL-13 genes on the 5q31-33, IL-3 À16T4C, IL-4 À590T4C, and IL-13 À1055C4T, with severity of malaria in 361 adult malaria patients in Thailand. The IL-13 À1055T allele showed a significant association with protection from severe malaria (OR 0.51, 95% CI 0.32-0.80; P ¼ 0.0032 by the w 2 test), while allele frequencies of IL-3 À16T4C and IL-4 À590T4C were not statistically different between mild and severe malaria patients. An IL-13 À1055C4T has been reported to alter the regulation of IL-13 production. Thus, IL-13 À1055T may show resistance to severe malaria through the alteration of IL-13 production.

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“…In addition to the genes encoding the T helper 2-type cytokines (the interleukin genes IL3, IL4, IL5, IL9, and IL13), there are also other immunologically active genes such as those encoding interferon regulatory factor-1 (IRF1), colony-stimulating factor-2 (CSF2), and T-cell transcription factor-7 (TCF7). Several studies have reported suggestive linkage to atopy and high serum total immunoglobulin (Ig) E levels [1][2][3], bronchial hyperresponsiveness [4], and blood eosinophilia [5,6], and association to asthma [7], but so far the results have remained mutually inconclusive. An international effort was made to define the markers spanning the 5q cytokine cluster by linkage analysis in a total of 11 retrospectively pooled data sets (1037 A Second-Generation Association Study of the 5q31 Cytokine Gene Cluster and the Interleukin-4 Receptor in Asthma IL4R, located on chromosome 16p12, is exceptionally polymorphic.…”

Section: Introductionmentioning

confidence: 99%

A Second-Generation Association Study of the 5q31 Cytokine Gene Cluster and the Interleukin-4 Receptor in Asthma

et al. 2001

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We have analyzed a dense set of single-nucleotide polymorphisms (SNPs) and microsatellites spanning the T-helper cytokine gene cluster (interleukins 3, 4, 5, 9, and 13, interferon regulatory factor-1, colony-stimulating factor-2, and T-cell transcription factor-7) on 5q31 and the gene encoding the interleukin-4 receptor (IL4R) on 16p12 among Finnish families with asthma. As shown by haplotype pattern mining analysis, the number of disease-associated haplotype patterns differed from that expected for the 129Q allele polymorphism in IL13 for high serum total immunoglobulin (Ig) E levels, but not for asthma. The same SNP also yielded the best haplotype associations. For IL4R, asthma-associated haplotype patterns, most spanning the S411L polymorphism, showed suggestive association. However, these haplotypes consisted of the major alleles for the intracellular part of the receptor and were very common among both patients and controls. The minor alleles 503P and 576R have been reported to be associated with decreased serum IgE levels and changes in the biological activity of the protein, especially when inherited together. In the Finnish population, these two polymorphisms segregated in strong linkage disequilibrium. Our data support previous findings regarding IL4R, indicating that 503P and 576R may act as minor protecting alleles for IgE-mediated disorders.Key Words: asthma, atopy, haplotype pattern mining, polymorphism, association families). The study showed suggestive linkage for asthma (LOD = 2.6) but no evidence for atopy [8]. Although it is not known whether human genes in the 5q31 cytokine cluster are genetic regulators for atopic disorders, experimental models of asthma have shown the importance of both IL4 and IL13 signaling. Administration of either exogenous IL4 or IL13 induced the asthma phenotype in mice [9]. However, neither of these cytokines was able to induce the asthma phenotype in mice deficient in the IL4 receptor (IL4R) [9]. The IL4 receptor is a heterodimer consisting of a common ␥-chain that is shared by several other interleukin receptors (IL2, IL7, IL9, and IL13) and a ligand-specific ␣-chain encoded by IL4R. An IL4R␣-IL13R␣ heterodimer is also able to transduce IL13 signaling [10] and is an important signaling pathway in the asthma model. All this indicates the importance of IL4R␣ in IL4/IL13-mediated signaling.

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Evidence for a Locus Regulating Total Serum IgE Levels Mapping to Chromosome 5

Cited by 374 publications

References 0 publications

A genome-wide linkage analysis of orchard grass-sensitive childhood seasonal allergic rhinitis in Japanese families

A genome-wide linkage analysis of orchard grass-sensitive childhood seasonal allergic rhinitis in Japanese families

A single-nucleotide substitution from C to T at position −1055 in the IL-13 promoter is associated with protection from severe malaria in Thailand

A Second-Generation Association Study of the 5q31 Cytokine Gene Cluster and the Interleukin-4 Receptor in Asthma

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