Asthma endophenotypes and polymorphisms in the histamine receptor HRH4 gene.
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.
Department of Immunology, Medical and Health Science Centre, University of Debrecen, Debrecen, Hungary. tundesim@gmail.com
Tünde
T
Simon
Agnes F
AF
Semsei
Ildikó
I
Ungvári
Eva
E
Hadadi
Viktor
V
Virág
Adrienne
A
Nagy
Mónika S
MS
Vangor
Valéria
V
László
Csaba
C
Szalai
András
A
Falus
D000293:Adolescent; D001249:Asthma / Q000209:etiology / Q000235:genetics*; D001483:Base Sequence; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D058068:Endophenotypes; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006801:Humans; D007239:Infections / Q000150:complications; D015810:Linkage Disequilibrium; D008297:Male; D020641:Polymorphism, Single Nucleotide; D043562:Receptors, G-Protein-Coupled / Q000235:genetics*; D011968:Receptors, Histamine / Q000235:genetics*; D000074040:Receptors, Histamine H4; D012307:Risk Factors; D055815:Young Adult
C418607:HRH4 protein, human; D043562:Receptors, G-Protein-Coupled; D011968:Receptors, Histamine; D000074040:Receptors, Histamine H4