Asthma Endophenotypes and Polymorphisms in the Histamine Receptor <b><i>HRH4</i></b> Gene

Abstract

Background: Histamine as an inflammatory mediator plays an important role in chronic allergic and asthmatic conditions. However, the role of genetic polymorphisms of the histamine receptor HRH4 (histamine receptor H4) gene in asthma susceptibility and endophenotypes has not been studied yet. Our aim was to investigate the possible association between single nucleotide polymorphisms (SNPs) in the HRH4 gene and asthma or some endophenotypes of asthma. Methods: Twenty-one SNPs of the HRH4 gene were genotyped in 313 asthmatic patients and 360 controls using Sequenom® iPLEX® Gold Genotyping Technology. Results: Genotype distribution of three HRH4 SNPs, namely rs17187619 [p = 0.002; odds ratio, OR (95% confidence interval, CI) = 2.4 (4.1–1.4)], rs527790 [p = 0.0002; OR (95% CI) = 3.3 (6.1–1.8)] and rs487202 [p = 0.00007; OR (95% CI) = 3.5 (6.6–1.9)] differed significantly between patients with or without infection-induced asthma. Haplotypes, which included the rs4800573–rs527790 CC allele combination, were found to be associated with infection-induced asthma [p = 0.0009, OR (95% CI) = 0.5 (0.4–0.8)]. The rs487202–rs574913 CA haplotype was more frequent among patients with infection-induced asthma [p = 0.0006, OR (95% CI) = 1.9 (1.3–2.6)]. None of the SNPs contributed directly to the risk of asthma. Conclusions: Our results suggest that genetic variation in the HRH4 gene might influence the pathogenesis of infection-induced asthma.

International Union of Basic and Clinical Pharmacology. XCVIII. Histamine Receptors

“…Along this line, keratinocytes derived from patients with atopic dermatitis expressed higher levels of the H 4 receptor mRNA compared with keratinocytes from patients without skin disease or psoriasis (Glatzer et al, 2013). In asthma, there appeared to be a link between three single nucleotide polymorphisms in the H 4 receptor gene and infectioninduced asthma (Simon et al, 2012). mRNA encoding the H 4 receptor was significantly higher expressed and H 4 receptor gene copy numbers were significantly amplified in patients with systemic lupus erythematosus compared with healthy controls.…”

Genetic variation associates with susceptibility for cigarette smoke-induced neutrophilia in mice

“…To date, little is known about the genetics of CS-induced neutrophilic airway inflammation, in contrast to the genetics of COPD or asthma for which many susceptibility genes have been identified (8,38). Although some studies have already investigated the genetics of emphysema in COPD as well as different endophenotypes of asthma (13,47), to our knowledge no studies investigating the genetics of CS-induced neutrophilic airway inflammation have been performed.…”

Genetic Variation Along The Histamine Pathway In Children With Allergic Vs. Non-Allergic Asthma

“…allergic asthma, exercise induced asthma). In their study, where allergic asthma was defined by environmental allergy skin prick testing, they also did not find an association between the HRH4 413C/T SNP and the disease [42]. However, they did identify an association between other variants, which were not included in our study (HRH4 rs527790, rs487202, rs17187619) and "infection-induced asthma".…”

“…Although the functional significance of many of these SNPs is unknown, several studies have been conducted to explore potential associations between histamine related genes and asthma and allergic disease [6,17,[33][34][35][36][37][38][39][40][41][42][43]. We have previously reported that the HRH1 gene was more highly expressed in buccal tissue from those with asthma compared to those without asthma [44].…”