title: Genetic variation within the histamine pathway among patients with asthma--a pilot study.
abstract: OBJECTIVE
  Histamine is an important mediator in the pathophysiology of asthma. We have previously reported that HRH1 is differentially expressed among those with asthma compared to those without asthma. Single histamine-related genes have also been associated with asthma. We aimed to evaluate known single nucleotide polymorphisms (SNPs) in genes along the histamine biotransformation and response pathway, and determine their association with asthma and HRH1 mRNA expression.
  
  
  METHODS
  We enrolled children and adults (n = 93) with/without asthma who met inclusion/exclusion criteria. Genotyping was performed for nine known SNPs in the HDC, HRH1, HRH4, HNMT and ABP1 genes. HRH1 mRNA expression was determined on RNA from buccal tissue. General linear model, Fisher's exact test and Chi-square test were used to determine differences in allele, genotype and haplotype frequency between subjects with and without asthma and differential HRH1 mRNA expression relative to genotype. Statistical significance was determined by p < 0.05.
  
  
  RESULTS
  No difference was observed in genotype/allele frequency for the nine SNPs between subjects with and without asthma. The HNMT-1639C/-464C/314C/3'UTRA haplotype was more frequently observed in those without asthma than those with asthma (p = 0.03). We also observed genetic differences relative to race and gender. HNMT 314 genotype CT was more frequent in males with asthma compared to those without asthma (p = 0.04).
  
  
  CONCLUSIONS
  Histamine pathway haplotype was associated with a diagnosis of asthma in our cohort but allele and genotype were not. Subgroup evaluations may also be important. Further studies are needed to determine the potential biological/clinical significance of our findings.
authors.affiliation: Division of Allergy/Asthma/Immunology .
authors.forename: Nikita
authors.initials: N
authors.lastname: Raje
authors.forename: Carrie A
authors.initials: CA
authors.lastname: Vyhlidal
authors.forename: Hongying
authors.initials: H
authors.lastname: Dai
authors.forename: Bridgette L
authors.initials: BL
authors.lastname: Jones
mesh_terms: D000328:Adult; D001741:Black or African American; D006631:Amine Oxidase (Copper-Containing) / Q000235:genetics; D001249:Asthma / Q000235:genetics*; D002648:Child; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D005838:Genotype; D006239:Haplotypes; D006632:Histamine / Q000378:metabolism*; D006801:Humans; D008297:Male; D010865:Pilot Projects; D020641:Polymorphism, Single Nucleotide; D012333:RNA, Messenger; D044469:Racial Groups; D043562:Receptors, G-Protein-Coupled / Q000235:genetics; D011968:Receptors, Histamine / Q000235:genetics; D000074040:Receptors, Histamine H4; D012737:Sex Factors; D044465:White People; D055815:Young Adult
chemical_list: C418607:HRH4 protein, human; D012333:RNA, Messenger; D043562:Receptors, G-Protein-Coupled; D011968:Receptors, Histamine; D000074040:Receptors, Histamine H4; D006632:Histamine; D006631:Amine Oxidase (Copper-Containing); C065976:AOC1 protein, human
keywords: ABP1; HDC; HNMT; HRH 1; HRH4; mRNA expression; single nucleotide polymorphisms