A functional CD86 polymorphism associated with asthma and related allergic disorders

Thomas Juhl Corydon, Annette Haagerup, Thomas Gryesten Jensen, Helle Glud Binderup, Mikkel Steen Petersen, Keld Kaltoft, Jørgen Vestbo, Torben Kruse, Anders Dupont Børglum

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Resumé

 
Udgivelsesdato: 2007-Aug
OriginalsprogEngelsk
TidsskriftJournal of Medical Genetics
Vol/bind44
Udgave nummer8
Sider (fra-til)509-515
Antal sider6
ISSN0022-2593
DOI
StatusUdgivet - 1. aug. 2007

Fingeraftryk

Alleles
Cytokine Receptors
Allergens
Hypersensitivity
Proteins
Parents
Amino Acids

Citer dette

Corydon, T. J., Haagerup, A., Jensen, T. G., Binderup, H. G., Petersen, M. S., Kaltoft, K., ... Børglum, A. D. (2007). A functional CD86 polymorphism associated with asthma and related allergic disorders. Journal of Medical Genetics, 44(8), 509-515. https://doi.org/10.1136/jmg.2007.049536
Corydon, Thomas Juhl ; Haagerup, Annette ; Jensen, Thomas Gryesten ; Binderup, Helle Glud ; Petersen, Mikkel Steen ; Kaltoft, Keld ; Vestbo, Jørgen ; Kruse, Torben ; Børglum, Anders Dupont. / A functional CD86 polymorphism associated with asthma and related allergic disorders. I: Journal of Medical Genetics. 2007 ; Bind 44, Nr. 8. s. 509-515.
@article{c1a05190ca8611dc8674000ea68e967b,
title = "A functional CD86 polymorphism associated with asthma and related allergic disorders",
abstract = "BACKGROUND: Several studies have documented a substantial genetic component in the aetiology of allergic diseases and a number of atopy susceptibility loci have been suggested. One of these loci is 3q21, at which linkage to multiple atopy phenotypes has been reported. This region harbours the CD86 gene encoding the costimulatory B7.2 protein. The costimulatory system, consisting of receptor proteins, cytokines and associated factors, activates T cells and regulates the immune response upon allergen challenge. METHODS: We sequenced the CD86 gene in patients with atopy from 10 families that showed evidence of linkage to 3q21. Identified polymorphisms were analysed in a subsequent family-based association study of two independent Danish samples, respectively comprising 135 and 100 trios of children with atopy and their parents. Functional analysis of the costimulatory effect on cytokine production was performed in an autologous cell-based system based on cells expressing CD86 variants. RESULTS: Two polymorphisms were identified, encoding the amino acid changes Ile179Val and Ala304Thr, respectively. Significant associations were observed between the Ile179Val polymorphism and allergy phenotypes in both samples (eg, asthma, p = 4 x 10(-3) in the two samples combined). The undertransmitted (protective) Val179 allele was found to induce higher production of both Th1 and Th2 cytokines than the overtransmitted (risk) Ile179 allele, suggesting a functional impact of the polymorphism. CONCLUSION: The CD86 gene, and specifically the Ile179Val polymorphism, may be a novel aetiological factor in the development of asthma and related allergic disorders.",
keywords = "Amino Acid Substitution, Antigens, CD, Antigens, CD86, Asthma, Cell Line, Cell Line, Tumor, Chromosomes, Human, Pair 3, Cloning, Molecular, Female, Humans, Hypersensitivity, Linkage (Genetics), Male, Melanoma, Polymorphism, Genetic, Siblings, T-Lymphocytes, Variation (Genetics)",
author = "Corydon, {Thomas Juhl} and Annette Haagerup and Jensen, {Thomas Gryesten} and Binderup, {Helle Glud} and Petersen, {Mikkel Steen} and Keld Kaltoft and J{\o}rgen Vestbo and Torben Kruse and B{\o}rglum, {Anders Dupont}",
year = "2007",
month = "8",
day = "1",
doi = "10.1136/jmg.2007.049536",
language = "English",
volume = "44",
pages = "509--515",
journal = "Journal of Medical Genetics",
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A functional CD86 polymorphism associated with asthma and related allergic disorders. / Corydon, Thomas Juhl; Haagerup, Annette; Jensen, Thomas Gryesten; Binderup, Helle Glud; Petersen, Mikkel Steen; Kaltoft, Keld; Vestbo, Jørgen; Kruse, Torben; Børglum, Anders Dupont.

I: Journal of Medical Genetics, Bind 44, Nr. 8, 01.08.2007, s. 509-515.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

TY - JOUR

T1 - A functional CD86 polymorphism associated with asthma and related allergic disorders

AU - Corydon, Thomas Juhl

AU - Haagerup, Annette

AU - Jensen, Thomas Gryesten

AU - Binderup, Helle Glud

AU - Petersen, Mikkel Steen

AU - Kaltoft, Keld

AU - Vestbo, Jørgen

AU - Kruse, Torben

AU - Børglum, Anders Dupont

PY - 2007/8/1

Y1 - 2007/8/1

N2 - BACKGROUND: Several studies have documented a substantial genetic component in the aetiology of allergic diseases and a number of atopy susceptibility loci have been suggested. One of these loci is 3q21, at which linkage to multiple atopy phenotypes has been reported. This region harbours the CD86 gene encoding the costimulatory B7.2 protein. The costimulatory system, consisting of receptor proteins, cytokines and associated factors, activates T cells and regulates the immune response upon allergen challenge. METHODS: We sequenced the CD86 gene in patients with atopy from 10 families that showed evidence of linkage to 3q21. Identified polymorphisms were analysed in a subsequent family-based association study of two independent Danish samples, respectively comprising 135 and 100 trios of children with atopy and their parents. Functional analysis of the costimulatory effect on cytokine production was performed in an autologous cell-based system based on cells expressing CD86 variants. RESULTS: Two polymorphisms were identified, encoding the amino acid changes Ile179Val and Ala304Thr, respectively. Significant associations were observed between the Ile179Val polymorphism and allergy phenotypes in both samples (eg, asthma, p = 4 x 10(-3) in the two samples combined). The undertransmitted (protective) Val179 allele was found to induce higher production of both Th1 and Th2 cytokines than the overtransmitted (risk) Ile179 allele, suggesting a functional impact of the polymorphism. CONCLUSION: The CD86 gene, and specifically the Ile179Val polymorphism, may be a novel aetiological factor in the development of asthma and related allergic disorders.

AB - BACKGROUND: Several studies have documented a substantial genetic component in the aetiology of allergic diseases and a number of atopy susceptibility loci have been suggested. One of these loci is 3q21, at which linkage to multiple atopy phenotypes has been reported. This region harbours the CD86 gene encoding the costimulatory B7.2 protein. The costimulatory system, consisting of receptor proteins, cytokines and associated factors, activates T cells and regulates the immune response upon allergen challenge. METHODS: We sequenced the CD86 gene in patients with atopy from 10 families that showed evidence of linkage to 3q21. Identified polymorphisms were analysed in a subsequent family-based association study of two independent Danish samples, respectively comprising 135 and 100 trios of children with atopy and their parents. Functional analysis of the costimulatory effect on cytokine production was performed in an autologous cell-based system based on cells expressing CD86 variants. RESULTS: Two polymorphisms were identified, encoding the amino acid changes Ile179Val and Ala304Thr, respectively. Significant associations were observed between the Ile179Val polymorphism and allergy phenotypes in both samples (eg, asthma, p = 4 x 10(-3) in the two samples combined). The undertransmitted (protective) Val179 allele was found to induce higher production of both Th1 and Th2 cytokines than the overtransmitted (risk) Ile179 allele, suggesting a functional impact of the polymorphism. CONCLUSION: The CD86 gene, and specifically the Ile179Val polymorphism, may be a novel aetiological factor in the development of asthma and related allergic disorders.

KW - Amino Acid Substitution

KW - Antigens, CD

KW - Antigens, CD86

KW - Asthma

KW - Cell Line

KW - Cell Line, Tumor

KW - Chromosomes, Human, Pair 3

KW - Cloning, Molecular

KW - Female

KW - Humans

KW - Hypersensitivity

KW - Linkage (Genetics)

KW - Male

KW - Melanoma

KW - Polymorphism, Genetic

KW - Siblings

KW - T-Lymphocytes

KW - Variation (Genetics)

U2 - 10.1136/jmg.2007.049536

DO - 10.1136/jmg.2007.049536

M3 - Journal article

C2 - 17513529

VL - 44

SP - 509

EP - 515

JO - Journal of Medical Genetics

JF - Journal of Medical Genetics

SN - 0022-2593

IS - 8

ER -