GENETIC VARIATION ALONG THE HISTAMINE PATHWAY IN CHILDREN WITH ALLERGIC VS NON-ALLERGIC ASTHMA

Abstract

Rationale: Previous studies have suggested that antihistamines may be therapeutic in some patients with asthma. Variation in genes along the histamine production, response, and degradation pathway may be important in predicting response to antihistamines. We hypothesize that genetic variation in genes of the histamine pathway differs between children with allergic versus non-allergic asthma. Methods: Children 7-18 years of age (n=118) with asthma participated in this IRB-approved protocol and were classified as allergic (N = 68) or non-allergic (N = 50) based on allergy skin testing. DNA isolation and genotyping were performed for 10 SNPs within 4 genes (HDC, HNMT, ABP1, HRH1, HRH4) within the histamine pathway. Chi Square tests were used to test for associations between genotypes and allergic or non-allergic asthma among participants. Significance was determined by p <0.05. Results: We observed differences in genotype frequency between participants with allergic versus non-allergic asthma for 2 SNPs: HNMT-1639(rs6430764) (31% allergic with TT vs. 14% non-allergic with TT, p=0.04) and HNMT -464 (rs2071048) genotype (33% allergic with TT vs. 12% non-allergic with TT, p=0.03) after controlling for race. Differences in genotype frequency were also observed between allergic and non-allergic phenotypes in stratified analyses among African Americans. Conclusion: Genetic variants within the histamine pathway appear to be associated with an allergic versus non-allergic asthma phenotype. Further studies are needed to validate our findings in a larger cohort. There is also the need to determine the functional significance of identified SNPs and their impact on antihistamine response in patients with asthma and allergic disease.