Polymorphisms of two histamine-metabolizing enzymes genes and childhood allergic asthma: a case control study

Abstract

BackgroundHistamine-metabolizing enzymes (N-methyltransferase and amiloride binding protein 1) are responsible for histamine degradation, a biogenic amine involved in allergic inflammation. Genetic variants of HNMT and ABP1 genes were found to be associated with altered enzyme activity. We hypothesized that alleles leading to decreased enzyme activity and, therefore, decreased inactivation of histamine may be responsible for altered susceptibility to asthma.MethodsThe aim of this study was to analyze polymorphisms within the HNMT and ABP1 genes in the group of 149 asthmatic children and in the group of 156 healthy children. The genetic analysis involved four polymorphisms of the HNMT gene: rs2071048 (-1637T/C), rs11569723 (-411C/T), rs1801105 (Thr105Ile = 314C/T) and rs1050891 (1097A/T) and rs1049793 (His645Asp) polymorphism for ABP1 gene. Genotyping was performed with use of PCR-RFLP. Statistical analysis was performed using Statistica software; linkage disequilibrium analysis was done with use of Haploview software.ResultsWe found an association of TT genotype and T allele of Thr105Ile polymorphism of HNMT gene with asthma. For other polymorphisms for HNMT and ABP1 genes, we have not observed relationship with asthma although the statistical power for some SNPs might not have been sufficient to detect an association. In linkage disequilibrium analysis, moderate linkage was found between -1637C/T and -411C/T polymorphisms of HNMT gene. However, no significant differences in haplotype frequencies were found between the group of the patients and the control group.ConclusionsOur results indicate modifying influence of histamine N-methyltransferase functional polymorphism on the risk of asthma. The other HNMT polymorphisms and ABP1 functional polymorphism seem unlikely to affect the risk of asthma.

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

“…SNP in the HNMT gene, but not in ABP1 , significantly influenced the risk of asthma in a Polish population [18]. Polymorphisms in the HDC and SLC22A3 genes influenced the risk of both rhinitis and asthma [19].…”

Serum neurotrophin-3 and neurotrophin-4 levels are associated with asthma severity in children

“…Based on the 2002 GINA guidelines, asthma severity was categorised as mild, moderate or severe o6 months before inclusion in the study. Atopy was defined according to previously described criteria [8].…”

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

“…for HNMT 314 occurred more frequently among Caucasian asthmatic children when compared to healthy controls [43]. Conflicting reports exist among various ethnic groups and asthma phenotypes in relation to the HNMT 314 SNP and asthma [36,37,40,41].…”

“…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].…”