Soy isoflavones reduce asthma exacerbation in asthmatic patients with high PAI-1–producing genotypes

Seong H. Cho*, Ara Jo, Thomas Casale, Su J. Jeong, Seung Jae Hong, Joong K. Cho, Janet T. Holbrook, Rajesh Kumar, Lewis J Smith

*Corresponding author for this work

Research output: Contribution to journalArticle

Abstract

Background: The 4G4G genotype of plasminogen activator inhibitor 1 (PAI-1) is associated with increased plasma PAI-1 levels and poor asthma control. Previous studies suggest that soy isoflavones can reduce PAI-1 levels. Objective: We sought to investigate PAI-1 genotype-specific differences of the soy isoflavone response in asthma outcomes. Methods: A PAI-1 functional polymorphism (rs1799768, 4G5G) was characterized in subjects with poorly controlled asthma enrolled in a randomized clinical trial of soy isoflavones (n = 265). Genotype-specific treatment responses on asthma outcomes were compared between soy isoflavones and placebo. Normal human bronchial epithelial cells were cultured with or without TGF-β1, genistein, or both, and PAI-1 levels were measured. Results: The 4G4G/4G5G genotype was associated with a greater risk for allergy-related worsened asthma symptoms and eczema at baseline compared with the 5G5G genotype. There was a significant interaction between the genotype and soy isoflavone intervention on oral corticosteroid use for asthma exacerbation (P = .005). In a subgroup analysis soy isoflavones significantly reduced the use of oral corticosteroids (number of events/person-year) by 4-fold compared with placebo in the 4G4G/4G5G genotype (0.2 vs 0.8; relative risk, 0.28; P < .001) but not in the 5G5G genotype. Soy isoflavones reduced plasma PAI-1 levels compared with placebo. Genistein treatment reduced TGF-β1–induced PAI-1 production in normal human bronchial epithelial cells. Conclusions: This study demonstrates that soy isoflavone treatment provides a significant benefit in reducing the number of severe asthma exacerbations in asthmatic patients with the high PAI-1–producing genotype. PAI-1 polymorphisms can be used as a genetic biomarker for soy isoflavone–responsive patients with asthma.

Original languageEnglish (US)
Pages (from-to)109-117.e4
JournalJournal of Allergy and Clinical Immunology
Volume144
Issue number1
DOIs
StatePublished - Jul 1 2019

Fingerprint

Isoflavones
Plasminogen Activator Inhibitor 1
Asthma
Genotype
Genistein
Placebos
Adrenal Cortex Hormones
Epithelial Cells
Eczema
Hypersensitivity
Therapeutics
Randomized Controlled Trials
Biomarkers

Keywords

  • Soy isoflavones
  • asthma
  • exacerbation
  • genistein
  • plasminogen activator inhibitor 1
  • polymorphisms

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Cho, Seong H. ; Jo, Ara ; Casale, Thomas ; Jeong, Su J. ; Hong, Seung Jae ; Cho, Joong K. ; Holbrook, Janet T. ; Kumar, Rajesh ; Smith, Lewis J. / Soy isoflavones reduce asthma exacerbation in asthmatic patients with high PAI-1–producing genotypes. In: Journal of Allergy and Clinical Immunology. 2019 ; Vol. 144, No. 1. pp. 109-117.e4.
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abstract = "Background: The 4G4G genotype of plasminogen activator inhibitor 1 (PAI-1) is associated with increased plasma PAI-1 levels and poor asthma control. Previous studies suggest that soy isoflavones can reduce PAI-1 levels. Objective: We sought to investigate PAI-1 genotype-specific differences of the soy isoflavone response in asthma outcomes. Methods: A PAI-1 functional polymorphism (rs1799768, 4G5G) was characterized in subjects with poorly controlled asthma enrolled in a randomized clinical trial of soy isoflavones (n = 265). Genotype-specific treatment responses on asthma outcomes were compared between soy isoflavones and placebo. Normal human bronchial epithelial cells were cultured with or without TGF-β1, genistein, or both, and PAI-1 levels were measured. Results: The 4G4G/4G5G genotype was associated with a greater risk for allergy-related worsened asthma symptoms and eczema at baseline compared with the 5G5G genotype. There was a significant interaction between the genotype and soy isoflavone intervention on oral corticosteroid use for asthma exacerbation (P = .005). In a subgroup analysis soy isoflavones significantly reduced the use of oral corticosteroids (number of events/person-year) by 4-fold compared with placebo in the 4G4G/4G5G genotype (0.2 vs 0.8; relative risk, 0.28; P < .001) but not in the 5G5G genotype. Soy isoflavones reduced plasma PAI-1 levels compared with placebo. Genistein treatment reduced TGF-β1–induced PAI-1 production in normal human bronchial epithelial cells. Conclusions: This study demonstrates that soy isoflavone treatment provides a significant benefit in reducing the number of severe asthma exacerbations in asthmatic patients with the high PAI-1–producing genotype. PAI-1 polymorphisms can be used as a genetic biomarker for soy isoflavone–responsive patients with asthma.",
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Soy isoflavones reduce asthma exacerbation in asthmatic patients with high PAI-1–producing genotypes. / Cho, Seong H.; Jo, Ara; Casale, Thomas; Jeong, Su J.; Hong, Seung Jae; Cho, Joong K.; Holbrook, Janet T.; Kumar, Rajesh; Smith, Lewis J.

In: Journal of Allergy and Clinical Immunology, Vol. 144, No. 1, 01.07.2019, p. 109-117.e4.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Soy isoflavones reduce asthma exacerbation in asthmatic patients with high PAI-1–producing genotypes

AU - Cho, Seong H.

AU - Jo, Ara

AU - Casale, Thomas

AU - Jeong, Su J.

AU - Hong, Seung Jae

AU - Cho, Joong K.

AU - Holbrook, Janet T.

AU - Kumar, Rajesh

AU - Smith, Lewis J

PY - 2019/7/1

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N2 - Background: The 4G4G genotype of plasminogen activator inhibitor 1 (PAI-1) is associated with increased plasma PAI-1 levels and poor asthma control. Previous studies suggest that soy isoflavones can reduce PAI-1 levels. Objective: We sought to investigate PAI-1 genotype-specific differences of the soy isoflavone response in asthma outcomes. Methods: A PAI-1 functional polymorphism (rs1799768, 4G5G) was characterized in subjects with poorly controlled asthma enrolled in a randomized clinical trial of soy isoflavones (n = 265). Genotype-specific treatment responses on asthma outcomes were compared between soy isoflavones and placebo. Normal human bronchial epithelial cells were cultured with or without TGF-β1, genistein, or both, and PAI-1 levels were measured. Results: The 4G4G/4G5G genotype was associated with a greater risk for allergy-related worsened asthma symptoms and eczema at baseline compared with the 5G5G genotype. There was a significant interaction between the genotype and soy isoflavone intervention on oral corticosteroid use for asthma exacerbation (P = .005). In a subgroup analysis soy isoflavones significantly reduced the use of oral corticosteroids (number of events/person-year) by 4-fold compared with placebo in the 4G4G/4G5G genotype (0.2 vs 0.8; relative risk, 0.28; P < .001) but not in the 5G5G genotype. Soy isoflavones reduced plasma PAI-1 levels compared with placebo. Genistein treatment reduced TGF-β1–induced PAI-1 production in normal human bronchial epithelial cells. Conclusions: This study demonstrates that soy isoflavone treatment provides a significant benefit in reducing the number of severe asthma exacerbations in asthmatic patients with the high PAI-1–producing genotype. PAI-1 polymorphisms can be used as a genetic biomarker for soy isoflavone–responsive patients with asthma.

AB - Background: The 4G4G genotype of plasminogen activator inhibitor 1 (PAI-1) is associated with increased plasma PAI-1 levels and poor asthma control. Previous studies suggest that soy isoflavones can reduce PAI-1 levels. Objective: We sought to investigate PAI-1 genotype-specific differences of the soy isoflavone response in asthma outcomes. Methods: A PAI-1 functional polymorphism (rs1799768, 4G5G) was characterized in subjects with poorly controlled asthma enrolled in a randomized clinical trial of soy isoflavones (n = 265). Genotype-specific treatment responses on asthma outcomes were compared between soy isoflavones and placebo. Normal human bronchial epithelial cells were cultured with or without TGF-β1, genistein, or both, and PAI-1 levels were measured. Results: The 4G4G/4G5G genotype was associated with a greater risk for allergy-related worsened asthma symptoms and eczema at baseline compared with the 5G5G genotype. There was a significant interaction between the genotype and soy isoflavone intervention on oral corticosteroid use for asthma exacerbation (P = .005). In a subgroup analysis soy isoflavones significantly reduced the use of oral corticosteroids (number of events/person-year) by 4-fold compared with placebo in the 4G4G/4G5G genotype (0.2 vs 0.8; relative risk, 0.28; P < .001) but not in the 5G5G genotype. Soy isoflavones reduced plasma PAI-1 levels compared with placebo. Genistein treatment reduced TGF-β1–induced PAI-1 production in normal human bronchial epithelial cells. Conclusions: This study demonstrates that soy isoflavone treatment provides a significant benefit in reducing the number of severe asthma exacerbations in asthmatic patients with the high PAI-1–producing genotype. PAI-1 polymorphisms can be used as a genetic biomarker for soy isoflavone–responsive patients with asthma.

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KW - exacerbation

KW - genistein

KW - plasminogen activator inhibitor 1

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