Atopy and new-onset asthma in young Danish farmers and CD14, TLR2, and TLR4 genetic polymorphisms: a nested case-control study.

L A M Smit, S I M Bongers, H J T Ruven, G T Rijkers, I M Wouters, D Heederik, Ø Omland, T Sigsgaard

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Abstract

BACKGROUND: Evidence exists that exposure to high levels of microbial agents such as endotoxin in the farm environment decreases the risk of atopic sensitization. Genetic variation in innate immunity genes may modulate the response to microbial agents and thus influence susceptibility to asthma and atopy. OBJECTIVE: To study potential associations between single nucleotide polymorphisms (SNPs) in CD14, Toll-like receptor 2 (TLR2), and TLR4 genes, and atopy and new-onset asthma in young farmers. METHODS: A nested case-control study was conducted within a cohort of 1901 young Danish farmers. We genotyped 100 new-onset asthma cases and 88 control subjects for three CD14 SNPs, three TLR2 SNPs, and two TLR4 SNPs. Atopy at baseline (defined as a positive skin prick test to one or more common inhalant allergens) was found in 17 asthma cases (17.0%) and in 17 controls (19.3%). RESULTS: The CD14/-260T allele was significantly associated with less atopy [odds ratio (OR) 0.39; 95% confidence interval (CI) 0.21-0.72, additive genetic model], whereas the CD14/-651T allele was positively associated with atopy (OR 2.53; 95% CI 1.33-4.80). Similar results were obtained by haplotype analysis. Stratified analysis by farm childhood showed stronger effects of both CD14 SNPs on atopy among farmers who were born and raised on a farm, although no significant interaction was found. No associations between CD14, TLR2, or TLR4 genotypes and new-onset asthma were found. CONCLUSION: The CD14/-260 and CD14/-651 promoter polymorphisms are associated with atopy prevalence among young adults exposed to farm environments.
Udgivelsesdato: 2007-Nov
Original languageEnglish
JournalClinical and Experimental Allergy
Volume37
Pages (from-to)1602-8
Number of pages6
ISSN0954-7894
DOIs
Publication statusPublished - 2007
Externally publishedYes

Keywords

  • Adolescent
  • Adult
  • Agricultural Workers' Diseases
  • Antigens, CD14
  • Asthma
  • Case-Control Studies
  • Denmark
  • Female
  • Gene Frequency
  • Genotype
  • Haplotypes
  • Humans
  • Hypersensitivity, Immediate
  • Linkage Disequilibrium
  • Male
  • Odds Ratio
  • Polymorphism, Single Nucleotide
  • Promoter Regions (Genetics)
  • Questionnaires
  • Toll-Like Receptor 2
  • Toll-Like Receptor 4

Cite this

Smit, L. A. M., Bongers, S. I. M., Ruven, H. J. T., Rijkers, G. T., Wouters, I. M., Heederik, D., ... Sigsgaard, T. (2007). Atopy and new-onset asthma in young Danish farmers and CD14, TLR2, and TLR4 genetic polymorphisms: a nested case-control study. Clinical and Experimental Allergy, 37, 1602-8. https://doi.org/10.1111/j.1365-2222.2007.02831.x
Smit, L A M ; Bongers, S I M ; Ruven, H J T ; Rijkers, G T ; Wouters, I M ; Heederik, D ; Omland, Ø ; Sigsgaard, T. / Atopy and new-onset asthma in young Danish farmers and CD14, TLR2, and TLR4 genetic polymorphisms: a nested case-control study. In: Clinical and Experimental Allergy. 2007 ; Vol. 37. pp. 1602-8.
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title = "Atopy and new-onset asthma in young Danish farmers and CD14, TLR2, and TLR4 genetic polymorphisms: a nested case-control study.",
abstract = "BACKGROUND: Evidence exists that exposure to high levels of microbial agents such as endotoxin in the farm environment decreases the risk of atopic sensitization. Genetic variation in innate immunity genes may modulate the response to microbial agents and thus influence susceptibility to asthma and atopy. OBJECTIVE: To study potential associations between single nucleotide polymorphisms (SNPs) in CD14, Toll-like receptor 2 (TLR2), and TLR4 genes, and atopy and new-onset asthma in young farmers. METHODS: A nested case-control study was conducted within a cohort of 1901 young Danish farmers. We genotyped 100 new-onset asthma cases and 88 control subjects for three CD14 SNPs, three TLR2 SNPs, and two TLR4 SNPs. Atopy at baseline (defined as a positive skin prick test to one or more common inhalant allergens) was found in 17 asthma cases (17.0{\%}) and in 17 controls (19.3{\%}). RESULTS: The CD14/-260T allele was significantly associated with less atopy [odds ratio (OR) 0.39; 95{\%} confidence interval (CI) 0.21-0.72, additive genetic model], whereas the CD14/-651T allele was positively associated with atopy (OR 2.53; 95{\%} CI 1.33-4.80). Similar results were obtained by haplotype analysis. Stratified analysis by farm childhood showed stronger effects of both CD14 SNPs on atopy among farmers who were born and raised on a farm, although no significant interaction was found. No associations between CD14, TLR2, or TLR4 genotypes and new-onset asthma were found. CONCLUSION: The CD14/-260 and CD14/-651 promoter polymorphisms are associated with atopy prevalence among young adults exposed to farm environments. Udgivelsesdato: 2007-Nov",
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Atopy and new-onset asthma in young Danish farmers and CD14, TLR2, and TLR4 genetic polymorphisms: a nested case-control study. / Smit, L A M; Bongers, S I M; Ruven, H J T; Rijkers, G T; Wouters, I M; Heederik, D; Omland, Ø; Sigsgaard, T.

In: Clinical and Experimental Allergy, Vol. 37, 2007, p. 1602-8.

Research output: Contribution to journalJournal articleResearchpeer-review

TY - JOUR

T1 - Atopy and new-onset asthma in young Danish farmers and CD14, TLR2, and TLR4 genetic polymorphisms: a nested case-control study.

AU - Smit, L A M

AU - Bongers, S I M

AU - Ruven, H J T

AU - Rijkers, G T

AU - Wouters, I M

AU - Heederik, D

AU - Omland, Ø

AU - Sigsgaard, T

PY - 2007

Y1 - 2007

N2 - BACKGROUND: Evidence exists that exposure to high levels of microbial agents such as endotoxin in the farm environment decreases the risk of atopic sensitization. Genetic variation in innate immunity genes may modulate the response to microbial agents and thus influence susceptibility to asthma and atopy. OBJECTIVE: To study potential associations between single nucleotide polymorphisms (SNPs) in CD14, Toll-like receptor 2 (TLR2), and TLR4 genes, and atopy and new-onset asthma in young farmers. METHODS: A nested case-control study was conducted within a cohort of 1901 young Danish farmers. We genotyped 100 new-onset asthma cases and 88 control subjects for three CD14 SNPs, three TLR2 SNPs, and two TLR4 SNPs. Atopy at baseline (defined as a positive skin prick test to one or more common inhalant allergens) was found in 17 asthma cases (17.0%) and in 17 controls (19.3%). RESULTS: The CD14/-260T allele was significantly associated with less atopy [odds ratio (OR) 0.39; 95% confidence interval (CI) 0.21-0.72, additive genetic model], whereas the CD14/-651T allele was positively associated with atopy (OR 2.53; 95% CI 1.33-4.80). Similar results were obtained by haplotype analysis. Stratified analysis by farm childhood showed stronger effects of both CD14 SNPs on atopy among farmers who were born and raised on a farm, although no significant interaction was found. No associations between CD14, TLR2, or TLR4 genotypes and new-onset asthma were found. CONCLUSION: The CD14/-260 and CD14/-651 promoter polymorphisms are associated with atopy prevalence among young adults exposed to farm environments. Udgivelsesdato: 2007-Nov

AB - BACKGROUND: Evidence exists that exposure to high levels of microbial agents such as endotoxin in the farm environment decreases the risk of atopic sensitization. Genetic variation in innate immunity genes may modulate the response to microbial agents and thus influence susceptibility to asthma and atopy. OBJECTIVE: To study potential associations between single nucleotide polymorphisms (SNPs) in CD14, Toll-like receptor 2 (TLR2), and TLR4 genes, and atopy and new-onset asthma in young farmers. METHODS: A nested case-control study was conducted within a cohort of 1901 young Danish farmers. We genotyped 100 new-onset asthma cases and 88 control subjects for three CD14 SNPs, three TLR2 SNPs, and two TLR4 SNPs. Atopy at baseline (defined as a positive skin prick test to one or more common inhalant allergens) was found in 17 asthma cases (17.0%) and in 17 controls (19.3%). RESULTS: The CD14/-260T allele was significantly associated with less atopy [odds ratio (OR) 0.39; 95% confidence interval (CI) 0.21-0.72, additive genetic model], whereas the CD14/-651T allele was positively associated with atopy (OR 2.53; 95% CI 1.33-4.80). Similar results were obtained by haplotype analysis. Stratified analysis by farm childhood showed stronger effects of both CD14 SNPs on atopy among farmers who were born and raised on a farm, although no significant interaction was found. No associations between CD14, TLR2, or TLR4 genotypes and new-onset asthma were found. CONCLUSION: The CD14/-260 and CD14/-651 promoter polymorphisms are associated with atopy prevalence among young adults exposed to farm environments. Udgivelsesdato: 2007-Nov

KW - Adolescent

KW - Adult

KW - Agricultural Workers' Diseases

KW - Antigens, CD14

KW - Asthma

KW - Case-Control Studies

KW - Denmark

KW - Female

KW - Gene Frequency

KW - Genotype

KW - Haplotypes

KW - Humans

KW - Hypersensitivity, Immediate

KW - Linkage Disequilibrium

KW - Male

KW - Odds Ratio

KW - Polymorphism, Single Nucleotide

KW - Promoter Regions (Genetics)

KW - Questionnaires

KW - Toll-Like Receptor 2

KW - Toll-Like Receptor 4

U2 - 10.1111/j.1365-2222.2007.02831.x

DO - 10.1111/j.1365-2222.2007.02831.x

M3 - Journal article

VL - 37

SP - 1602

EP - 1608

JO - Clinical and Experimental Allergy

JF - Clinical and Experimental Allergy

SN - 0954-7894

ER -