Linkage of Asthma and Total Serum IgE Concentration to Markers on Chromosome 12q: Evidence from Afro-Caribbean and Caucasian Populations

Barnes, Kathleen C.; Neely, John D.; Duffy, David L.; Freidhoff, Linda R.; Breazeale, Daniel R.; Schou, C.; Naidu, Raana P.; Levett, Paul N.; Renault, Béatrice; Kucherlapati, Raju; Iozzino, Sebastiano; Ehrlich, Eva; Beaty, Terri H.; Marsh, David G.

doi:10.1006/geno.1996.0518

Cited by 222 publications

(170 citation statements)

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“…[7][8][9] IgE antibodies are largely responsible for triggering type 1 immediate-hypersensitivity reactions. In studies of food allergy there is little data relating clinical severity and IgE level.…”

Section: Discussionmentioning

confidence: 99%

“…6 A region on chromosome 12q has been shown to be linked with total serum IgE concentration and atopy in several different populations. [7][8][9] STAT6 is a central molecule in the signal transduction pathway used by IL-4 and IL-13 in IgE isotype switching and production of TH2 cytokines. [10][11][12] In STAT6-deficient mice it has been observed that most IL-4-mediated functions are reduced.…”

Section: Introductionmentioning

confidence: 99%

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Polymorphism in the STAT6 gene encodes risk for nut allergy

et al. 2002

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Polymorphism in the STAT6 gene encodes risk for nut allergy

et al. 2002

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“…The chromosome 12 region was initially described by a candidate region approach [Barnes et al, 1996;Nickel et al, 1997;Wilkinson et al, are included and are shown in bold and italics. All linkage data of the fine mapping are available via the internet (http://cooke.gsf.de/asthmagen).…”

Section: Discussionmentioning

confidence: 99%

“…Nitric oxide is synthesized by three isoforms of NO synthases [Stuehr, 1999]. NOS1 consists of 29 exons and is located on chromosome 12q24.2-q24.31 [Barnes et al, 1996]. The analyzed SNPs are located in exon 18 (3391C>T) and the 3′UTR (5266C>T) of the NOS1 gene.…”

Section: Introductionmentioning

confidence: 99%

Fine mapping and single nucleotide polymorphism association results of candidate genes for asthma and related phenotypes

et al. 2001

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Several genome-wide screens for asthma and related phenotypes have been published to date but data on fine-mapping are scarce. For higher resolution we performed a fine-mapping study with 2 cM average spacing in often discussed asthma candidate regions (2p, 5q, 6p, 7p, 9q, 11p, and 12q) to narrow down the regions of interest. All participants of a Caucasian family study (97 families with at least two affected sib pairs) were genotyped for 49 supplementary polymorphic dinucleotide markers. Our results indicate increased evidence for linkage on chromosome 6p, 9q, and 12q. These candidate regions were further analyzed with SNP polymorphisms in the endothelin 1 (EDN1), lymphotoxin alpha (LTA), and neuronal nitric oxide synthase (NOS1) genes. In addition, IL4 -590C>T and IL10 -592C>A, localized on chromosomes 5q and 1q, respectively, have been analyzed for SNP association. Of the six SNPs tested, four revealed weak association with the examined phenotypes. These are the IL10 -592C>A SNP in the interleukin 10 gene (p=0.036 for eosinophil cell counts), the 4124T>C SNP in EDN1 (p=0.044 for asthma), the 3391C>T SNP in NOS1 with eosinophil cell counts (p=0.0086), and the 5266C>T polymorphism, also in the NOS1 gene, for high IgE levels (p=0.022). In summary, fine mapping data enable us to confine asthma candidate regions, while variants of EDN1 and NOS1, or nearby genes, may play an important role in this context. Hum Mutat 18:327 336, 2001.

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“…36 Several familiarity and genetic studies have indicated that heritable components control the serum levels of IgE, IgA and IgG [37][38][39] and identified a number of loci influencing total serum levels of these antibodies in humans. [40][41][42] There is also convincing evidence for parent-offspring effects and genetic heritability in human serum IgM levels [37][38][39] as well as evidence for genetic control of natural IgM titers in mammals, 43 birds 44 and fish. 45 However, no linkage evidence for quantitative trait loci influencing serum IgM has been reported and the genetics of the homeostatic regulation of serum IgM remains largely unknown.…”

Section: Introductionmentioning

confidence: 99%

Irf4 is a positional and functional candidate gene for the control of serum IgM levels in the mouse

et al. 2008

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Natural IgM are involved in numerous immunological functions but the genetic factors that control the homeostasis of its secretion and upholding remain unknown. Prompted by the finding that C57BL/6 mice had significantly lower serum levels of IgM when compared with BALB/c mice, we performed a genome-wide screen and found that the level of serum IgM was controlled by a QTL on chromosome 13 reaching the highest level of association at marker D13Mit266 (LOD score¼3.54). This locus was named IgMSC1 and covered a region encompassing the interferon-regulatory factor 4 gene (Irf4). The number of splenic mature B cells in C57BL/6 did not differ from BALB/c mice but we found that low serum levels of IgM in C57BL/6 mice correlated with lower frequency of IgM-secreting cells in the spleen and in the peritoneal cavity. These results suggested that C57BL/6 mice have lower efficiency in late B-cell maturation, a process that is highly impaired in Irf4 knockout mice. In fact, we also found reduced Irf4 gene expression in B cells of C57BL/6 mice. Thus, we propose Irf4 as a candidate for the IgMSC1 locus, which controls IgM homeostatic levels at the level of B-cell terminal differentiation

show abstract

Linkage of Asthma and Total Serum IgE Concentration to Markers on Chromosome 12q: Evidence from Afro-Caribbean and Caucasian Populations

Cited by 222 publications

References 3 publications

Polymorphism in the STAT6 gene encodes risk for nut allergy

Polymorphism in the STAT6 gene encodes risk for nut allergy

Fine mapping and single nucleotide polymorphism association results of candidate genes for asthma and related phenotypes

Irf4 is a positional and functional candidate gene for the control of serum IgM levels in the mouse

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