Genetic variation within the histamine pathway among patients with asthma--a pilot study.
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.
The Journal of asthma : official journal of the Association for the Care of Asthma
Adult; African Americans; Amine Oxidase (Copper-Containing); Asthma; Child; Continental Population Groups; European Continental Ancestry Group; Female; Gene Frequency; Genetic Predisposition to Disease; Genetic Variation; Genotype; Haplotypes; Histamine; Humans; Male; Pilot Projects; Polymorphism, Single Nucleotide; RNA, Messenger; Receptors, G-Protein-Coupled; Receptors, Histamine; Receptors, Histamine H4; Sex Factors; Young Adult
Amine Oxidase; Asthma; Gene Frequency; Genetic Predisposition to Disease; Genetic Variation; Genotype; Haplotypes; Histamine; Pilot Projects; Polymorphism, Single Nucleotide; G-Protein-Coupled Receptors; Histamine Receptors; Sex Factors
Raje, N., Vyhlidal, C. A., Dai, H., Jones, B. L. Genetic variation within the histamine pathway among patients with asthma--a pilot study. The Journal of asthma : official journal of the Association for the Care of Asthma 52, 353-362 (2015).