HMOX1 and GST variants modify attenuation of FEF25-75% decline due to PM10 reduction

I. Curjuric; M. Imboden; C. Schindler; S. H. Downs; M. Hersberger; S. L. J. Liu; G. Matyas; E. W. Russi; J. Schwartz; G. A. Thun; D. S. Postma; T. Rochat; N. M. Probst-Hensch; SAPALDIA Team

doi:10.1183/09031936.00044309

HMOX1 and GST variants modify attenuation of FEF25-75% decline due to PM10 reduction

I. Curjuric, M. Imboden, C. Schindler, S. H. Downs, M. Hersberger, S. L. J. Liu, G. Matyas, E. W. Russi, J. Schwartz, G. A. Thun, D. S. Postma, T. Rochat, N. M. Probst-Hensch^*, SAPALDIA Team

^*Corresponding author for this work

Groningen Research Institute for Asthma and COPD (GRIAC)

Research output: Contribution to journal › Article › Academic › peer-review

27 Citations (Scopus)

Abstract

Reduced exposure to particulate matter with a 50% cut-off aerodynamic diameter of 10 mu m (PM(10)) attenuated age-related lung function decline in our cohort, particularly in the small airways. We hypothesised that polymorphisms in glutathione S-transferase (GST) and haem oxygenase-1 (HMOX1) genes, important for oxidative stress defence, modify these beneficial effects.

A population-based sample of 4,365 adults was followed up after 11 yrs, including questionnaire, spirometry and DNA blood sampling. PM(10) exposure was estimated by dispersion modelling and temporal interpolation. The main effects on annual decline in forced expiratory flow at 25-75% of forced vital capacity (FEF(25-75%)) and interactions with PM(10) reduction were investigated for polymorphisms HMOX1 rs2071746 (T/A), rs735266 (T/A) and rs5995098 (G/C), HMOX1 (GT)(n) promoter repeat, GSTM1 and GSTT1 deletions, and GSTP1 p.lle105Val, using mixed linear regression models.

HMOX1 rs5995098, HMOX1 haplotype TTG and GSTP1 showed significant genetic main effects. Interactions with PM(10) reduction were detected: a 10 mu g.m(-3) reduction significantly attenuated annual FEF(25-75%) decline by 15.3 mL.s(-1) only in the absence of HMOX1 haplotype ATC. Similarly, carriers of long (GT)(n) promoter repeat alleles or the GSTP1 Val/Val genotype profited significantly more from a 10 mu g.m(-3) reduction (26.5 mL.s(-1) and 27.3 mL.s(-1) respectively) than non-carriers.

Benefits of a reduction in PM(10) exposure are not equally distributed across the population but are modified by the individual genetic make-up determining oxidative stress defence.

Original language	English
Pages (from-to)	505-514
Number of pages	10
Journal	European Respiratory Journal
Volume	35
Issue number	3
DOIs	https://doi.org/10.1183/09031936.00044309
Publication status	Published - Mar-2010

Keywords

Exposure to particles with a 50% cut-off aerodynamic diameter of 10 mu m
forced expiratory flow at 25-75% of forced vital capacity
general population sample
glutathione S-transferase
haem oxygenase-1
lung function decline
LUNG-FUNCTION DECLINE
RESPIRATORY-HEALTH-SURVEY
S-TRANSFERASE P1
AIR-POLLUTION
HAPLOTYPE RECONSTRUCTION
GENERAL-POPULATION
HEME OXYGENASE-1
SWISS COHORT
GLUTATHIONE
SAPALDIA

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Curjuric, I., Imboden, M., Schindler, C., Downs, S. H., Hersberger, M., Liu, S. L. J., Matyas, G., Russi, E. W., Schwartz, J., Thun, G. A., Postma, D. S., Rochat, T., Probst-Hensch, N. M., & SAPALDIA Team (2010). HMOX1 and GST variants modify attenuation of FEF25-75% decline due to PM10 reduction. European Respiratory Journal, 35(3), 505-514. https://doi.org/10.1183/09031936.00044309

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title = "HMOX1 and GST variants modify attenuation of FEF25-75% decline due to PM10 reduction",

abstract = "Reduced exposure to particulate matter with a 50% cut-off aerodynamic diameter of 10 mu m (PM(10)) attenuated age-related lung function decline in our cohort, particularly in the small airways. We hypothesised that polymorphisms in glutathione S-transferase (GST) and haem oxygenase-1 (HMOX1) genes, important for oxidative stress defence, modify these beneficial effects.A population-based sample of 4,365 adults was followed up after 11 yrs, including questionnaire, spirometry and DNA blood sampling. PM(10) exposure was estimated by dispersion modelling and temporal interpolation. The main effects on annual decline in forced expiratory flow at 25-75% of forced vital capacity (FEF(25-75%)) and interactions with PM(10) reduction were investigated for polymorphisms HMOX1 rs2071746 (T/A), rs735266 (T/A) and rs5995098 (G/C), HMOX1 (GT)(n) promoter repeat, GSTM1 and GSTT1 deletions, and GSTP1 p.lle105Val, using mixed linear regression models.HMOX1 rs5995098, HMOX1 haplotype TTG and GSTP1 showed significant genetic main effects. Interactions with PM(10) reduction were detected: a 10 mu g.m(-3) reduction significantly attenuated annual FEF(25-75%) decline by 15.3 mL.s(-1) only in the absence of HMOX1 haplotype ATC. Similarly, carriers of long (GT)(n) promoter repeat alleles or the GSTP1 Val/Val genotype profited significantly more from a 10 mu g.m(-3) reduction (26.5 mL.s(-1) and 27.3 mL.s(-1) respectively) than non-carriers.Benefits of a reduction in PM(10) exposure are not equally distributed across the population but are modified by the individual genetic make-up determining oxidative stress defence.",

keywords = "Exposure to particles with a 50% cut-off aerodynamic diameter of 10 mu m, forced expiratory flow at 25-75% of forced vital capacity, general population sample, glutathione S-transferase, haem oxygenase-1, lung function decline, LUNG-FUNCTION DECLINE, RESPIRATORY-HEALTH-SURVEY, S-TRANSFERASE P1, AIR-POLLUTION, HAPLOTYPE RECONSTRUCTION, GENERAL-POPULATION, HEME OXYGENASE-1, SWISS COHORT, GLUTATHIONE, SAPALDIA",

author = "I. Curjuric and M. Imboden and C. Schindler and Downs, {S. H.} and M. Hersberger and Liu, {S. L. J.} and G. Matyas and Russi, {E. W.} and J. Schwartz and Thun, {G. A.} and Postma, {D. S.} and T. Rochat and Probst-Hensch, {N. M.} and {SAPALDIA Team}",

year = "2010",

month = mar,

doi = "10.1183/09031936.00044309",

language = "English",

volume = "35",

pages = "505--514",

journal = "European Respiratory Journal",

issn = "0903-1936",

publisher = "EUROPEAN RESPIRATORY SOC JOURNALS LTD",

number = "3",

}

Curjuric, I, Imboden, M, Schindler, C, Downs, SH, Hersberger, M, Liu, SLJ, Matyas, G, Russi, EW, Schwartz, J, Thun, GA, Postma, DS, Rochat, T, Probst-Hensch, NM & SAPALDIA Team 2010, 'HMOX1 and GST variants modify attenuation of FEF25-75% decline due to PM10 reduction', European Respiratory Journal, vol. 35, no. 3, pp. 505-514. https://doi.org/10.1183/09031936.00044309

TY - JOUR

T1 - HMOX1 and GST variants modify attenuation of FEF25-75% decline due to PM10 reduction

AU - Curjuric, I.

AU - Imboden, M.

AU - Schindler, C.

AU - Downs, S. H.

AU - Hersberger, M.

AU - Liu, S. L. J.

AU - Matyas, G.

AU - Russi, E. W.

AU - Schwartz, J.

AU - Thun, G. A.

AU - Postma, D. S.

AU - Rochat, T.

AU - Probst-Hensch, N. M.

AU - SAPALDIA Team

PY - 2010/3

Y1 - 2010/3

N2 - Reduced exposure to particulate matter with a 50% cut-off aerodynamic diameter of 10 mu m (PM(10)) attenuated age-related lung function decline in our cohort, particularly in the small airways. We hypothesised that polymorphisms in glutathione S-transferase (GST) and haem oxygenase-1 (HMOX1) genes, important for oxidative stress defence, modify these beneficial effects.A population-based sample of 4,365 adults was followed up after 11 yrs, including questionnaire, spirometry and DNA blood sampling. PM(10) exposure was estimated by dispersion modelling and temporal interpolation. The main effects on annual decline in forced expiratory flow at 25-75% of forced vital capacity (FEF(25-75%)) and interactions with PM(10) reduction were investigated for polymorphisms HMOX1 rs2071746 (T/A), rs735266 (T/A) and rs5995098 (G/C), HMOX1 (GT)(n) promoter repeat, GSTM1 and GSTT1 deletions, and GSTP1 p.lle105Val, using mixed linear regression models.HMOX1 rs5995098, HMOX1 haplotype TTG and GSTP1 showed significant genetic main effects. Interactions with PM(10) reduction were detected: a 10 mu g.m(-3) reduction significantly attenuated annual FEF(25-75%) decline by 15.3 mL.s(-1) only in the absence of HMOX1 haplotype ATC. Similarly, carriers of long (GT)(n) promoter repeat alleles or the GSTP1 Val/Val genotype profited significantly more from a 10 mu g.m(-3) reduction (26.5 mL.s(-1) and 27.3 mL.s(-1) respectively) than non-carriers.Benefits of a reduction in PM(10) exposure are not equally distributed across the population but are modified by the individual genetic make-up determining oxidative stress defence.

AB - Reduced exposure to particulate matter with a 50% cut-off aerodynamic diameter of 10 mu m (PM(10)) attenuated age-related lung function decline in our cohort, particularly in the small airways. We hypothesised that polymorphisms in glutathione S-transferase (GST) and haem oxygenase-1 (HMOX1) genes, important for oxidative stress defence, modify these beneficial effects.A population-based sample of 4,365 adults was followed up after 11 yrs, including questionnaire, spirometry and DNA blood sampling. PM(10) exposure was estimated by dispersion modelling and temporal interpolation. The main effects on annual decline in forced expiratory flow at 25-75% of forced vital capacity (FEF(25-75%)) and interactions with PM(10) reduction were investigated for polymorphisms HMOX1 rs2071746 (T/A), rs735266 (T/A) and rs5995098 (G/C), HMOX1 (GT)(n) promoter repeat, GSTM1 and GSTT1 deletions, and GSTP1 p.lle105Val, using mixed linear regression models.HMOX1 rs5995098, HMOX1 haplotype TTG and GSTP1 showed significant genetic main effects. Interactions with PM(10) reduction were detected: a 10 mu g.m(-3) reduction significantly attenuated annual FEF(25-75%) decline by 15.3 mL.s(-1) only in the absence of HMOX1 haplotype ATC. Similarly, carriers of long (GT)(n) promoter repeat alleles or the GSTP1 Val/Val genotype profited significantly more from a 10 mu g.m(-3) reduction (26.5 mL.s(-1) and 27.3 mL.s(-1) respectively) than non-carriers.Benefits of a reduction in PM(10) exposure are not equally distributed across the population but are modified by the individual genetic make-up determining oxidative stress defence.

KW - Exposure to particles with a 50% cut-off aerodynamic diameter of 10 mu m

KW - forced expiratory flow at 25-75% of forced vital capacity

KW - general population sample

KW - glutathione S-transferase

KW - haem oxygenase-1

KW - lung function decline

KW - LUNG-FUNCTION DECLINE

KW - RESPIRATORY-HEALTH-SURVEY

KW - S-TRANSFERASE P1

KW - AIR-POLLUTION

KW - HAPLOTYPE RECONSTRUCTION

KW - GENERAL-POPULATION

KW - HEME OXYGENASE-1

KW - SWISS COHORT

KW - GLUTATHIONE

KW - SAPALDIA

U2 - 10.1183/09031936.00044309

DO - 10.1183/09031936.00044309

M3 - Article

SN - 0903-1936

VL - 35

SP - 505

EP - 514

JO - European Respiratory Journal

JF - European Respiratory Journal

IS - 3

ER -

HMOX1 and GST variants modify attenuation of FEF25-75% decline due to PM10 reduction

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Keywords

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