Genetic variation along the histamine pathway in children with allergic versus nonallergic asthma

Sara Anvari, Carrie A. Vyhlidal, Hongying Dai, Bridgette L. Jones

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

Histamine is an important mediator in the pathogenesis of asthma. Variation in genes along the histamine production, response, and degradation pathway may be important in predicting response to antihistamines. We hypothesize that differences exist among singlenucleotide polymorphisms (SNPs) in genes of the histamine pathway between children with allergic versus nonallergic asthma. Children (7-18 yr of age; n = 202) with asthma were classified as allergic or nonallergic based on allergy skin testing. Genotyping was performed to detect known SNPs (n = 10) among genes (HDC, HNMT, ABP1, HRH1, and HRH4) within the histamine pathway. Chi square tests and Cochran-Armitage Trend were used to identify associations between genetic variants and allergic or nonallergic asthma. Significance was determined by P,0.05 and false-positive report probability. After correction for race differences in genotype were observed, HRH1-17 TT (6% allergic versus 0% nonallergic; P = 0.04), HNMT-464 TT (41% allergic versus 29% nonallergic; P = 0.04), and HNMT-1639 TT (30% allergic versus 20% nonallergic; P = 0.04) were overrepresented among children with allergic asthma. Genotype differences specifically among the African-American children were also observed: HRH1-17 TT (13% allergic versus 0% nonallergic; P = 0.04) and HNMT-1639 TT (23% allergic versus 3% nonallergic; P = 0.03) genotypes were overrepresented among African-American children with allergic asthma. Our study suggests that genetic variation within the histamine pathway may be associated with an allergic versus nonallergic asthma phenotype. Further studies are needed to determine the functional significance of identified SNPs and their impact on antihistamine response in patients with asthma and allergic disease.

Original languageEnglish (US)
Pages (from-to)802-809
Number of pages8
JournalAmerican journal of respiratory cell and molecular biology
Volume53
Issue number6
DOIs
StatePublished - Dec 2015

Fingerprint

Histamine
Asthma
Polymorphism
Genes
Histamine Antagonists
Genotype
Allergies
African Americans
Skin
Chi-Square Distribution
Degradation
Testing
Hypersensitivity
Phenotype

Keywords

  • Asthma
  • Genetics
  • Histamine

ASJC Scopus subject areas

  • Molecular Biology
  • Pulmonary and Respiratory Medicine
  • Clinical Biochemistry
  • Cell Biology

Cite this

Genetic variation along the histamine pathway in children with allergic versus nonallergic asthma. / Anvari, Sara; Vyhlidal, Carrie A.; Dai, Hongying; Jones, Bridgette L.

In: American journal of respiratory cell and molecular biology, Vol. 53, No. 6, 12.2015, p. 802-809.

Research output: Contribution to journalArticle

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abstract = "Histamine is an important mediator in the pathogenesis of asthma. Variation in genes along the histamine production, response, and degradation pathway may be important in predicting response to antihistamines. We hypothesize that differences exist among singlenucleotide polymorphisms (SNPs) in genes of the histamine pathway between children with allergic versus nonallergic asthma. Children (7-18 yr of age; n = 202) with asthma were classified as allergic or nonallergic based on allergy skin testing. Genotyping was performed to detect known SNPs (n = 10) among genes (HDC, HNMT, ABP1, HRH1, and HRH4) within the histamine pathway. Chi square tests and Cochran-Armitage Trend were used to identify associations between genetic variants and allergic or nonallergic asthma. Significance was determined by P,0.05 and false-positive report probability. After correction for race differences in genotype were observed, HRH1-17 TT (6{\%} allergic versus 0{\%} nonallergic; P = 0.04), HNMT-464 TT (41{\%} allergic versus 29{\%} nonallergic; P = 0.04), and HNMT-1639 TT (30{\%} allergic versus 20{\%} nonallergic; P = 0.04) were overrepresented among children with allergic asthma. Genotype differences specifically among the African-American children were also observed: HRH1-17 TT (13{\%} allergic versus 0{\%} nonallergic; P = 0.04) and HNMT-1639 TT (23{\%} allergic versus 3{\%} nonallergic; P = 0.03) genotypes were overrepresented among African-American children with allergic asthma. Our study suggests that genetic variation within the histamine pathway may be associated with an allergic versus nonallergic asthma phenotype. Further studies are needed to determine the functional significance of identified SNPs and their impact on antihistamine response in patients with asthma and allergic disease.",
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