Family based association analysis of the IL2 and IL15 genes in allergic disorders

Ulla Christensen, Annette Haagerup, Helle G Binderup, Jørgen Vestbo, Torben A Kruse, Anders D Børglum

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Resumé

Allergic diseases affect an increasing number of individuals and are a major global health problem. A substantial genetic contribution in the aetiology of allergic diseases is well documented. We have previously reported linkage of allergic diseases and atopy to the region harbouring the IL2 gene (4q27). IL15 is located approximately 20 Mb distal to IL2. The two genes encode cytokines that are structurally and functionally related, both inducing T-cell activation and proliferation. We screened the two genes for sequence variation and applied the seven single-nucleotide polymorphisms (SNPs) identified in a family based association study of two Danish samples comprising a total of 235 families with allergic diseases. None of the IL15 SNPs showed significant association and the haplotype analysis yielded inconsistent results in the two samples. In contrast, the two IL2 SNPs showed association both separately and in haplotypes with several atopic phenotypes, most significantly with IgE-mediated allergy. (single SNP P-value 0.0005 for positive skin prick test, haplotype P-value 0.019 for positive RAST test). To our knowledge, this is the first study reporting association between IL2 and IgE-mediated allergy, asthma and atopic eczema. The SNP (rs2069762) that showed the most consistent results is located in the promoter and has previously been shown to influence the level of IL2 expression. We suggest that the observed overtransmission of the T allele of this SNP may convey increased susceptibility to allergic disease by skewing the Th1/Th2 balance towards Th2.

OriginalsprogEngelsk
TidsskriftEuropean Journal of Human Genetics
Vol/bind14
Udgave nummer2
Sider (fra-til)227-35
Antal sider9
ISSN1018-4813
DOI
StatusUdgivet - feb. 2006

Fingeraftryk

Interleukin-15
Interleukin-2
Single Nucleotide Polymorphism
Haplotypes
Hypersensitivity
Th1-Th2 Balance
Atopic Dermatitis
Alleles
Cell Proliferation

Citer dette

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abstract = "Allergic diseases affect an increasing number of individuals and are a major global health problem. A substantial genetic contribution in the aetiology of allergic diseases is well documented. We have previously reported linkage of allergic diseases and atopy to the region harbouring the IL2 gene (4q27). IL15 is located approximately 20 Mb distal to IL2. The two genes encode cytokines that are structurally and functionally related, both inducing T-cell activation and proliferation. We screened the two genes for sequence variation and applied the seven single-nucleotide polymorphisms (SNPs) identified in a family based association study of two Danish samples comprising a total of 235 families with allergic diseases. None of the IL15 SNPs showed significant association and the haplotype analysis yielded inconsistent results in the two samples. In contrast, the two IL2 SNPs showed association both separately and in haplotypes with several atopic phenotypes, most significantly with IgE-mediated allergy. (single SNP P-value 0.0005 for positive skin prick test, haplotype P-value 0.019 for positive RAST test). To our knowledge, this is the first study reporting association between IL2 and IgE-mediated allergy, asthma and atopic eczema. The SNP (rs2069762) that showed the most consistent results is located in the promoter and has previously been shown to influence the level of IL2 expression. We suggest that the observed overtransmission of the T allele of this SNP may convey increased susceptibility to allergic disease by skewing the Th1/Th2 balance towards Th2.",
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Family based association analysis of the IL2 and IL15 genes in allergic disorders. / Christensen, Ulla; Haagerup, Annette; Binderup, Helle G; Vestbo, Jørgen; Kruse, Torben A; Børglum, Anders D.

I: European Journal of Human Genetics, Bind 14, Nr. 2, 02.2006, s. 227-35.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

TY - JOUR

T1 - Family based association analysis of the IL2 and IL15 genes in allergic disorders

AU - Christensen, Ulla

AU - Haagerup, Annette

AU - Binderup, Helle G

AU - Vestbo, Jørgen

AU - Kruse, Torben A

AU - Børglum, Anders D

PY - 2006/2

Y1 - 2006/2

N2 - Allergic diseases affect an increasing number of individuals and are a major global health problem. A substantial genetic contribution in the aetiology of allergic diseases is well documented. We have previously reported linkage of allergic diseases and atopy to the region harbouring the IL2 gene (4q27). IL15 is located approximately 20 Mb distal to IL2. The two genes encode cytokines that are structurally and functionally related, both inducing T-cell activation and proliferation. We screened the two genes for sequence variation and applied the seven single-nucleotide polymorphisms (SNPs) identified in a family based association study of two Danish samples comprising a total of 235 families with allergic diseases. None of the IL15 SNPs showed significant association and the haplotype analysis yielded inconsistent results in the two samples. In contrast, the two IL2 SNPs showed association both separately and in haplotypes with several atopic phenotypes, most significantly with IgE-mediated allergy. (single SNP P-value 0.0005 for positive skin prick test, haplotype P-value 0.019 for positive RAST test). To our knowledge, this is the first study reporting association between IL2 and IgE-mediated allergy, asthma and atopic eczema. The SNP (rs2069762) that showed the most consistent results is located in the promoter and has previously been shown to influence the level of IL2 expression. We suggest that the observed overtransmission of the T allele of this SNP may convey increased susceptibility to allergic disease by skewing the Th1/Th2 balance towards Th2.

AB - Allergic diseases affect an increasing number of individuals and are a major global health problem. A substantial genetic contribution in the aetiology of allergic diseases is well documented. We have previously reported linkage of allergic diseases and atopy to the region harbouring the IL2 gene (4q27). IL15 is located approximately 20 Mb distal to IL2. The two genes encode cytokines that are structurally and functionally related, both inducing T-cell activation and proliferation. We screened the two genes for sequence variation and applied the seven single-nucleotide polymorphisms (SNPs) identified in a family based association study of two Danish samples comprising a total of 235 families with allergic diseases. None of the IL15 SNPs showed significant association and the haplotype analysis yielded inconsistent results in the two samples. In contrast, the two IL2 SNPs showed association both separately and in haplotypes with several atopic phenotypes, most significantly with IgE-mediated allergy. (single SNP P-value 0.0005 for positive skin prick test, haplotype P-value 0.019 for positive RAST test). To our knowledge, this is the first study reporting association between IL2 and IgE-mediated allergy, asthma and atopic eczema. The SNP (rs2069762) that showed the most consistent results is located in the promoter and has previously been shown to influence the level of IL2 expression. We suggest that the observed overtransmission of the T allele of this SNP may convey increased susceptibility to allergic disease by skewing the Th1/Th2 balance towards Th2.

KW - DNA Primers

KW - Denmark

KW - Family

KW - Gene Frequency

KW - Genotype

KW - Haplotypes

KW - Humans

KW - Hypersensitivity

KW - Interleukin-15

KW - Interleukin-2

KW - Linkage Disequilibrium

KW - Polymorphism, Single Nucleotide

KW - Sequence Analysis, DNA

KW - Comparative Study

KW - Journal Article

KW - Research Support, Non-U.S. Gov't

U2 - 10.1038/sj.ejhg.5201541

DO - 10.1038/sj.ejhg.5201541

M3 - Journal article

C2 - 16333313

VL - 14

SP - 227

EP - 235

JO - European Journal of Human Genetics

JF - European Journal of Human Genetics

SN - 1018-4813

IS - 2

ER -