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

The 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.We 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.Our 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.Histamine is a preformed mediator released during mast cell degranulation that plays a key role in the development of allergic inflammation and, subsequently, leads to atopic diseases such as bronchial asthma. Released histamine is metabolized by two enzymes: N-methyltransferase (HNMT) and diamine oxidase (amiloride binding protein 1, ABP1).N-methylation catalyzed by cytosolic HNMT enzyme is the primary pathway for histamine bio-transformation in bronchial epithelium [1]. HNMT gene is located on the chromosome 2q22.1 and within the gene region, several polymorphisms have been identified. A common C314T polymorphism leading to Thr105Ile substitution was