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Single nucleotide polymorphisms and haplotypes of histamine <Emphasis Type="Italic">N</Emphasis>-methyltransferase in patients with gastric ulcer
Authors:G?-L?Chen  B?Zhu  W?-P?Nie  Z?-H?Xu  Z?-R?Tan  G?Zhou  J?Liu  W?Wang  Email author" target="_blank">H?-H?ZhouEmail author
Institution:(1) Pharmacogenetics Research Institute, Institute of Clinical Pharmacology, Central South University, Changsha, Hunan, 410078, P.R. China;(2) 3rd Xiang-Ya Hospital of Central South University, Changsha, Hunan, 410013, P.R. China;(3) Clinical Drug Evaluation, Johnson & Johnson Pharmacoceutical Research & Development, LLC, 920 Route 202 South Raritan, NJ 08869, USA;(4) Department of Pathology, HEB, Medical College of Ohio, Rm 202, 3055 Arlington Ave, Toledo, OH, 43614-5806, USA
Abstract:Introduction: Histamine plays a crucial role in the regulation of gastric acid secretion, which is involved in the pathogenesis of peptic ulcer. Histamine N-methyltransferase (HNMT) is the major metabolizing enzyme for histamine inactivation in human stomach.Objective: This study aims to determine whether there exists a relationship between HNMT gene polymorphisms and the risk for gastric ulcer (GU).Methods: 118 GU patients and 154 ethnically matched control subjects were enrolled and polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assays were developed to genotype all these subjects for the T-1637C, C-411T, C314T and A1097T point mutations in HNMT gene. Haplotypes were reconstructed from the genotype data.Results: Frequencies of the variant alleles in cases and controls were 0.398 vs 0.396 for T-1637C, 0.144 vs 0.110 for C-411T, 0.034 vs 0.042 for C314T, and 0.242 vs 0.273 for A1097T, respectively, with no significant difference for any locus between the two groups (all P > 0.05). Also the frequencies of genotypes, haplotypes and haplotype pairs based on these polymorphisms did not differ significantly between cases and controls.Conclusion: This study provided no evidence for the involvement of HNMT polymorphisms in the susceptibility to GU.Received 5 February 2004; returned for revision 10 March 2004; accepted by A. Falus 22 April 2004
Keywords:Gastric ulcer  Histamine N-methyltransferase  Single nucleotide polymorphism  Haplotype  Case-control study
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