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 9 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 9 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.

Histamine H4 receptor gene polymorphisms: a potential contributor to Meniere disease

“…For example, in a study that was conducted in the US, Caucasians have a higher prevalence than other major ethnicities, including Hispanics, Blacks, and Asians [34]. Given that histamine H1 receptor expression exhibits genetic differences relative to race [35], we cannot rule out the possibility that there are racial predispositions to HRH4 rs77485247 polymorphism in MD patients. Hence, further study will be needed to validate our findings in a larger and more diverse population of patients.…”

Genetic Variation in the Histamine Production, Response, and Degradation Pathway Is Associated with Histamine Pharmacodynamic Response in Children with Asthma

“…We did not observe an association between histamine genetic variation and non-phenotyped asthma. However, histamine pathway genotype was associated with the allergic asthma phenotype (Anvari et al, 2015; Raje et al, 2015). As 50–80% of those with asthma are reported to have allergic asthma, understanding the contributions of histamine and genetic variation within the histamine pathway are important.…”

Plasma Inflammatory Cytokine IL-4, IL-8, IL-10, and TNF-α Levels Correlate with Pulmonary Function in Patients with Asthma-Chronic Obstructive Pulmonary Disease (COPD) Overlap Syndrome

“…As a chronic inflammatory respiratory disease, asthma is characterized by episodic bronchoconstriction and airway hyper-responsiveness to a variety of stimuli, such as viral antigens, allergens, and environmental exposures, and may cause shortness of breath, chest tightness, coughing, and wheezing [ 1 ]. It has been reported that 25.9 million (8.5%) people in the United States had asthma in 2011, including 7.0 million children, with increasing prevalence rates [ 2 ].…”