title: Genetic Variation along the Histamine Pathway in Children with Allergic versus Nonallergic Asthma.
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 single-nucleotide 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.
authors.affiliation: 1 Division of Allergy/Asthma/Immunology.|2 Children's Mercy Hospital, and.|3 University of Missouri Kansas City, Kansas City, Missouri.
authors.forename: Sara
authors.initials: S
authors.lastname: Anvari
authors.affiliation: 4 Division of Pediatric Clinical Pharmacology and Therapeutic Innovation.|2 Children's Mercy Hospital, and.|3 University of Missouri Kansas City, Kansas City, Missouri.
authors.forename: Carrie A
authors.initials: CA
authors.lastname: Vyhlidal
authors.affiliation: 5 Research Development and Clinical Investigation.|2 Children's Mercy Hospital, and.|3 University of Missouri Kansas City, Kansas City, Missouri.
authors.forename: Hongying
authors.initials: H
authors.lastname: Dai
authors.affiliation: 1 Division of Allergy/Asthma/Immunology.|4 Division of Pediatric Clinical Pharmacology and Therapeutic Innovation.|2 Children's Mercy Hospital, and.|3 University of Missouri Kansas City, Kansas City, Missouri.
authors.forename: Bridgette L
authors.initials: BL
authors.lastname: Jones
mesh_terms: D000293:Adolescent; D001741:Black or African American; D006631:Amine Oxidase (Copper-Containing) / Q000235:genetics*; D001249:Asthma / Q000208:ethnology / Q000235:genetics* / Q000276:immunology; D002648:Child; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006632:Histamine / Q000502:physiology*; D006637:Histamine N-Methyltransferase / Q000235:genetics*; D006801:Humans; D008297:Male; D020641:Polymorphism, Single Nucleotide; D011968:Receptors, Histamine / Q000235:genetics*; D015398:Signal Transduction; D044465:White People
chemical_list: D011968:Receptors, Histamine; D006632:Histamine; D006631:Amine Oxidase (Copper-Containing); C065976:AOC1 protein, human; D006637:Histamine N-Methyltransferase
keywords: asthma; genetics; histamine