Single nucleotide polymorphisms and haplotypes of histamine N-methyltransferase in patients with gastric ulcer

Chen, G. L.; Zhu, Bing; Nie, Wei; Xu, Zhen; Tan, Zhi‐Rong; Zhou, Gangqiao; Liu, Jie; Wang, W.; Zhou, Hong‐Hao

doi:10.1007/s00011-004-1290-0

Cited by 12 publications

(4 citation statements)

References 33 publications

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“…The other SNPs from the 5’-flanking region (-1637T/C, -463T/C, -411C/T) as well as 3’UTR (939A/G and 1097A/T) of HNMT gene have been also reported [13], however their functionality has not been well described yet. The region containing -411C/T polymorphism is located in a positive regulatory sequence between nucleotides -493 and -395 [22].…”

Section: Discussionmentioning

confidence: 99%

“…The HNMT and ABP1 polymorphisms were analyzed by PCR-RFLP method. The conditions of PCR-RFLP and sequences of the primers for the HNMT polymorphisms (-1637C/T, -411C/T, 314C/T and 1097A/T) were used as described previously [13]. For ABP1 His645Asp polymorphism, the genotyping was performed according to conditions described by Garcia-Martin et al [14].…”

Section: Methodsmentioning

confidence: 99%

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

et al. 2010

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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.

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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

et al. 2010

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“…Because histamine plays a prominent role in the pathogenesis of allergic diseases, it has been hypothesized that individuals carrying variant alleles leading to a decreased inactivation of histamine may show altered susceptibility or a different evolution of such diseases. In this regard, promising findings indicating the association of the HNMT Thr105Ile polymorphism with asthma were initially reported [12], although further independent studies failed to identify such an association for patients with asthma or bronchial hyperresponsiveness [13, 14] or other pathologies related to histamine such as ASA‐induced urticaria/angio‐oedema [15], ulcerative colitis [16] or gastric ulcer [17].…”

Section: Introductionmentioning

confidence: 99%

Polymorphisms of histamine‐metabolizing enzymes and clinical manifestations of asthma and allergic rhinitis

García‐Martín

García-Menaya

Sánchez

et al. 2007

Clin Experimental Allergy

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“…The T105I polymorphism was initially thought to be associated with an increased risk of asthma and inflammation (25). However, recent studies have shown no link between the 105I allele and asthma (26)(27)(28) or gastric inflammation (29). Interestingly, it is the more active 105T protein that appears to be associated with disease.…”

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confidence: 99%

The Histamine N-Methyltransferase T105I Polymorphism Affects Active Site Structure and Dynamics

2007

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Histamine N-methyltransferase (HNMT) is the sole enzyme responsible for inactivating histamine in the mammalian brain. The human HNMT gene contains a common threonine-isoleucine polymorphism at residue 105, distal from the active site. The 105I variant has decreased activity and lower protein levels relative to the 105T protein. Crystal structures of both variants have been solved, but reveal little regarding how the T105I polymorphism affects activity. We performed molecular dynamics simulations of both 105T and 105I at 37°C to explore the structural and dynamic consequences of the polymorphism. The simulations indicate that replacing Thr with the larger Ile residue leads to greater burial of residue 105 and heightened packing interactions between residue105 and residues within helix α3 and strand β3. This altered packing is directly translated to the active site resulting in the reorientation of several co-substrate-binding residues. The simulations also show that the hydrophobic histamine-binding domain in both proteins undergoes a large-scale breathing motion that exposes key catalytic residues and lessens the hydrophobicity of the substrate-binding site.

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Single nucleotide polymorphisms and haplotypes of histamine N-methyltransferase in patients with gastric ulcer

Abstract: This study provided no evidence for the involvement of HNMT polymorphisms in the susceptibility to GU.

Cited by 12 publications

References 33 publications

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

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

Polymorphisms of histamine‐metabolizing enzymes and clinical manifestations of asthma and allergic rhinitis

The Histamine N-Methyltransferase T105I Polymorphism Affects Active Site Structure and Dynamics

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