Genetic variants of IL-13 signalling and human asthma and atopy

A. Heinzmann, X. Q. Mao, M. Akaiwa, R. T. Kreomer, P. S. Gao, K. Ohshima, R. Umeshita, Y. Abe, S. Braun, T. Yamashita, M. H. Roberts, R. Sugimoto, K. Arima, Y. Arinobu, B. Yu, S. Kruse, T. Enomoto, Y. Dake, M. Kawai, S. ShimazuS. Sasaki, C. N. Adra, M. Kitaichi, H. Inoue, K. Yamauchi, N. Tomichi, F. Kurimoto, N. Hamasaki, J. M. Hopkin, K. Izuhara, T. Shirakawa, K. A. Deichmann

研究成果: ジャーナルへの寄稿記事

370 引用 (Scopus)

抄録

Asthma and atopy show epidemiological association and are biologically linked by T-helper type 2 (T(h)2) cytokine-driven inflammatory mechanisms. IL-4 operates through the IL-4 receptor (IL-4R, a heterodimer of IL-4Rα and either γc or IL-13Rα1) and IL-13 operates through IL-13R (a heterodimer of IL-4Ra and IL-13Rα1) to promote IgE synthesis and IgE-based mucosal inflammation which typify atopy. Recent animal model data suggest that IL-13 is a central cytokine in promoting asthma, through the stimulation of bronchial epithelial mucus secretion and smooth muscle hyper-reactivity. We investigated the role of common genetic variants of IL-13 and IL-13Rα1 in human asthma, considering IgE levels. A novel variant of human IL-13, Gln110Arg, on chromosome 5q31, associated with asthma rather than IgE levels in case-control populations from Britain and Japan [peak odds ratio (OR) = 2.31, 95% CI 1.33-4.00]; the variant also predicted asthma and higher serum IL-13 levels in a general, Japanese paediatric population. Immunohistochemistry demonstrated that both subunits of IL-13R are prominently expressed in bronchial epithelium and smooth muscle from asthmatic subjects. Detailed molecular modelling analyses indicate that residue 110 of IL-13, the site of the charge-modifying variants Arg and Gln, is important in the internal constitution of the ligand and crucial in ligand-receptor interaction. A non-coding variant of IL-13Rα1, A1398G, on chromosome Xq13, associated primarily with high IgE levels (OR = 3.38 in males, 1.10 in females) rather than asthma. Thus, certain variants of IL-13 signalling are likely to be important promoters of human asthma; detailed functional analysis of their actions is needed.

元の言語英語
ページ(範囲)549-559
ページ数11
ジャーナルHuman Molecular Genetics
9
発行部数4
出版物ステータス出版済み - 3 1 2000

Fingerprint

Interleukin-13
Asthma
Immunoglobulin E
Smooth Muscle
Chromosomes
Odds Ratio
Interleukin-4 Receptors
Cytokines
Ligands
Constitution and Bylaws
Mucus
human interleukin-13
Interleukin-4
Population
Japan
Epithelium
Animal Models
Immunohistochemistry
Pediatrics
Inflammation

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Genetics
  • Genetics(clinical)

これを引用

Heinzmann, A., Mao, X. Q., Akaiwa, M., Kreomer, R. T., Gao, P. S., Ohshima, K., ... Deichmann, K. A. (2000). Genetic variants of IL-13 signalling and human asthma and atopy. Human Molecular Genetics, 9(4), 549-559.

Genetic variants of IL-13 signalling and human asthma and atopy. / Heinzmann, A.; Mao, X. Q.; Akaiwa, M.; Kreomer, R. T.; Gao, P. S.; Ohshima, K.; Umeshita, R.; Abe, Y.; Braun, S.; Yamashita, T.; Roberts, M. H.; Sugimoto, R.; Arima, K.; Arinobu, Y.; Yu, B.; Kruse, S.; Enomoto, T.; Dake, Y.; Kawai, M.; Shimazu, S.; Sasaki, S.; Adra, C. N.; Kitaichi, M.; Inoue, H.; Yamauchi, K.; Tomichi, N.; Kurimoto, F.; Hamasaki, N.; Hopkin, J. M.; Izuhara, K.; Shirakawa, T.; Deichmann, K. A.

:: Human Molecular Genetics, 巻 9, 番号 4, 01.03.2000, p. 549-559.

研究成果: ジャーナルへの寄稿記事

Heinzmann, A, Mao, XQ, Akaiwa, M, Kreomer, RT, Gao, PS, Ohshima, K, Umeshita, R, Abe, Y, Braun, S, Yamashita, T, Roberts, MH, Sugimoto, R, Arima, K, Arinobu, Y, Yu, B, Kruse, S, Enomoto, T, Dake, Y, Kawai, M, Shimazu, S, Sasaki, S, Adra, CN, Kitaichi, M, Inoue, H, Yamauchi, K, Tomichi, N, Kurimoto, F, Hamasaki, N, Hopkin, JM, Izuhara, K, Shirakawa, T & Deichmann, KA 2000, 'Genetic variants of IL-13 signalling and human asthma and atopy', Human Molecular Genetics, 巻. 9, 番号 4, pp. 549-559.
Heinzmann A, Mao XQ, Akaiwa M, Kreomer RT, Gao PS, Ohshima K その他. Genetic variants of IL-13 signalling and human asthma and atopy. Human Molecular Genetics. 2000 3 1;9(4):549-559.
Heinzmann, A. ; Mao, X. Q. ; Akaiwa, M. ; Kreomer, R. T. ; Gao, P. S. ; Ohshima, K. ; Umeshita, R. ; Abe, Y. ; Braun, S. ; Yamashita, T. ; Roberts, M. H. ; Sugimoto, R. ; Arima, K. ; Arinobu, Y. ; Yu, B. ; Kruse, S. ; Enomoto, T. ; Dake, Y. ; Kawai, M. ; Shimazu, S. ; Sasaki, S. ; Adra, C. N. ; Kitaichi, M. ; Inoue, H. ; Yamauchi, K. ; Tomichi, N. ; Kurimoto, F. ; Hamasaki, N. ; Hopkin, J. M. ; Izuhara, K. ; Shirakawa, T. ; Deichmann, K. A. / Genetic variants of IL-13 signalling and human asthma and atopy. :: Human Molecular Genetics. 2000 ; 巻 9, 番号 4. pp. 549-559.
@article{800e28eb000746408724ee4181645f98,
title = "Genetic variants of IL-13 signalling and human asthma and atopy",
abstract = "Asthma and atopy show epidemiological association and are biologically linked by T-helper type 2 (T(h)2) cytokine-driven inflammatory mechanisms. IL-4 operates through the IL-4 receptor (IL-4R, a heterodimer of IL-4Rα and either γc or IL-13Rα1) and IL-13 operates through IL-13R (a heterodimer of IL-4Ra and IL-13Rα1) to promote IgE synthesis and IgE-based mucosal inflammation which typify atopy. Recent animal model data suggest that IL-13 is a central cytokine in promoting asthma, through the stimulation of bronchial epithelial mucus secretion and smooth muscle hyper-reactivity. We investigated the role of common genetic variants of IL-13 and IL-13Rα1 in human asthma, considering IgE levels. A novel variant of human IL-13, Gln110Arg, on chromosome 5q31, associated with asthma rather than IgE levels in case-control populations from Britain and Japan [peak odds ratio (OR) = 2.31, 95{\%} CI 1.33-4.00]; the variant also predicted asthma and higher serum IL-13 levels in a general, Japanese paediatric population. Immunohistochemistry demonstrated that both subunits of IL-13R are prominently expressed in bronchial epithelium and smooth muscle from asthmatic subjects. Detailed molecular modelling analyses indicate that residue 110 of IL-13, the site of the charge-modifying variants Arg and Gln, is important in the internal constitution of the ligand and crucial in ligand-receptor interaction. A non-coding variant of IL-13Rα1, A1398G, on chromosome Xq13, associated primarily with high IgE levels (OR = 3.38 in males, 1.10 in females) rather than asthma. Thus, certain variants of IL-13 signalling are likely to be important promoters of human asthma; detailed functional analysis of their actions is needed.",
author = "A. Heinzmann and Mao, {X. Q.} and M. Akaiwa and Kreomer, {R. T.} and Gao, {P. S.} and K. Ohshima and R. Umeshita and Y. Abe and S. Braun and T. Yamashita and Roberts, {M. H.} and R. Sugimoto and K. Arima and Y. Arinobu and B. Yu and S. Kruse and T. Enomoto and Y. Dake and M. Kawai and S. Shimazu and S. Sasaki and Adra, {C. N.} and M. Kitaichi and H. Inoue and K. Yamauchi and N. Tomichi and F. Kurimoto and N. Hamasaki and Hopkin, {J. M.} and K. Izuhara and T. Shirakawa and Deichmann, {K. A.}",
year = "2000",
month = "3",
day = "1",
language = "English",
volume = "9",
pages = "549--559",
journal = "Human Molecular Genetics",
issn = "0964-6906",
publisher = "Oxford University Press",
number = "4",

}

TY - JOUR

T1 - Genetic variants of IL-13 signalling and human asthma and atopy

AU - Heinzmann, A.

AU - Mao, X. Q.

AU - Akaiwa, M.

AU - Kreomer, R. T.

AU - Gao, P. S.

AU - Ohshima, K.

AU - Umeshita, R.

AU - Abe, Y.

AU - Braun, S.

AU - Yamashita, T.

AU - Roberts, M. H.

AU - Sugimoto, R.

AU - Arima, K.

AU - Arinobu, Y.

AU - Yu, B.

AU - Kruse, S.

AU - Enomoto, T.

AU - Dake, Y.

AU - Kawai, M.

AU - Shimazu, S.

AU - Sasaki, S.

AU - Adra, C. N.

AU - Kitaichi, M.

AU - Inoue, H.

AU - Yamauchi, K.

AU - Tomichi, N.

AU - Kurimoto, F.

AU - Hamasaki, N.

AU - Hopkin, J. M.

AU - Izuhara, K.

AU - Shirakawa, T.

AU - Deichmann, K. A.

PY - 2000/3/1

Y1 - 2000/3/1

N2 - Asthma and atopy show epidemiological association and are biologically linked by T-helper type 2 (T(h)2) cytokine-driven inflammatory mechanisms. IL-4 operates through the IL-4 receptor (IL-4R, a heterodimer of IL-4Rα and either γc or IL-13Rα1) and IL-13 operates through IL-13R (a heterodimer of IL-4Ra and IL-13Rα1) to promote IgE synthesis and IgE-based mucosal inflammation which typify atopy. Recent animal model data suggest that IL-13 is a central cytokine in promoting asthma, through the stimulation of bronchial epithelial mucus secretion and smooth muscle hyper-reactivity. We investigated the role of common genetic variants of IL-13 and IL-13Rα1 in human asthma, considering IgE levels. A novel variant of human IL-13, Gln110Arg, on chromosome 5q31, associated with asthma rather than IgE levels in case-control populations from Britain and Japan [peak odds ratio (OR) = 2.31, 95% CI 1.33-4.00]; the variant also predicted asthma and higher serum IL-13 levels in a general, Japanese paediatric population. Immunohistochemistry demonstrated that both subunits of IL-13R are prominently expressed in bronchial epithelium and smooth muscle from asthmatic subjects. Detailed molecular modelling analyses indicate that residue 110 of IL-13, the site of the charge-modifying variants Arg and Gln, is important in the internal constitution of the ligand and crucial in ligand-receptor interaction. A non-coding variant of IL-13Rα1, A1398G, on chromosome Xq13, associated primarily with high IgE levels (OR = 3.38 in males, 1.10 in females) rather than asthma. Thus, certain variants of IL-13 signalling are likely to be important promoters of human asthma; detailed functional analysis of their actions is needed.

AB - Asthma and atopy show epidemiological association and are biologically linked by T-helper type 2 (T(h)2) cytokine-driven inflammatory mechanisms. IL-4 operates through the IL-4 receptor (IL-4R, a heterodimer of IL-4Rα and either γc or IL-13Rα1) and IL-13 operates through IL-13R (a heterodimer of IL-4Ra and IL-13Rα1) to promote IgE synthesis and IgE-based mucosal inflammation which typify atopy. Recent animal model data suggest that IL-13 is a central cytokine in promoting asthma, through the stimulation of bronchial epithelial mucus secretion and smooth muscle hyper-reactivity. We investigated the role of common genetic variants of IL-13 and IL-13Rα1 in human asthma, considering IgE levels. A novel variant of human IL-13, Gln110Arg, on chromosome 5q31, associated with asthma rather than IgE levels in case-control populations from Britain and Japan [peak odds ratio (OR) = 2.31, 95% CI 1.33-4.00]; the variant also predicted asthma and higher serum IL-13 levels in a general, Japanese paediatric population. Immunohistochemistry demonstrated that both subunits of IL-13R are prominently expressed in bronchial epithelium and smooth muscle from asthmatic subjects. Detailed molecular modelling analyses indicate that residue 110 of IL-13, the site of the charge-modifying variants Arg and Gln, is important in the internal constitution of the ligand and crucial in ligand-receptor interaction. A non-coding variant of IL-13Rα1, A1398G, on chromosome Xq13, associated primarily with high IgE levels (OR = 3.38 in males, 1.10 in females) rather than asthma. Thus, certain variants of IL-13 signalling are likely to be important promoters of human asthma; detailed functional analysis of their actions is needed.

UR - http://www.scopus.com/inward/record.url?scp=0034162827&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0034162827&partnerID=8YFLogxK

M3 - Article

C2 - 10699178

AN - SCOPUS:0034162827

VL - 9

SP - 549

EP - 559

JO - Human Molecular Genetics

JF - Human Molecular Genetics

SN - 0964-6906

IS - 4

ER -