title: Histamine N-methyltransferase gene polymorphisms in Chinese and their relationship with enzyme activity in erythrocytes.
abstract: The aim of this study was to identify polymorphisms in the histamine N-methyltransferase (HNMT) gene in Chinese and to assess their relationship with HNMT activity. One hundred and ninety-two unrelated subjects were recruited. HNMT polymorphisms were screened by direct sequencing with purified polymerase chain reaction products comprising all six exons, plus splice junctions, as well as approximately 2 kb of the 5'-flanking region (5'-FR). Erythrocyte HNMT activity was previously measured by radiochemical microassay. A total of 11 single nucleotide polymorphisms (SNPs) were identified, among which six SNPs had variant allele frequencies greater than 5%. Of the six common SNPs, three (-1637T>C, -463T>C and -411C>T) were located in 5'-FR, one (314C>T) in coding exons, and two (939A>G and 1097A>T) in the 3'-untranslated region (3'-UTR). Most of these common SNPs were in linkage disequilibrium. Genotype-phenotype correlation analyses were performed for those common SNPs in 5'-FR and 3'-UTR. In males, no significant association was found between HNMT activity and these non-coding SNPs. However, in females, the -1637T>C or -463T>C tended to be associated with decreased HNMT activity, whereas the 939A>G or 1097A>T appeared to be correlated with increased enzymatic activity. HNMT polymorphisms differ considerably between Chinese and American. The common SNPs in 5'-FR (-1637T>C and -463T>C) and 3'-UTR (939A>G and 1097A>T) might conditionally regulate the activity of HNMT, or might be genetically linked to unknown mutation(s) underlying the HNMT phenotypic variance.
authors.affiliation: Pharmacogenetics Research Institute, Institute of Clinical Pharmacology, Central South University, Changsha, PR China.
authors.forename: Guo-Lin
authors.initials: GL
authors.lastname: Chen
authors.forename: Haijian
authors.initials: H
authors.lastname: Wang
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.forename: Zhen-Hua
authors.initials: ZH
authors.lastname: Xu
authors.forename: Gan
authors.initials: G
authors.lastname: Zhou
authors.forename: Fuchu
authors.initials: F
authors.lastname: He
authors.forename: Hong-Hao
authors.initials: HH
authors.lastname: Zhou
mesh_terms: D020413:3' Untranslated Regions; D024506:5' Flanking Region; D000293:Adolescent; D000328:Adult; D000483:Alleles; D044466:Asian People / Q000235:genetics*; D002681:China; D004912:Erythrocytes / Q000201:enzymology*; D005260:Female; D005787:Gene Frequency; D005820:Genetic Testing; D014644:Genetic Variation; D006239:Haplotypes; D006637:Histamine N-Methyltransferase / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D011110:Polymorphism, Genetic; D012150:Polymorphism, Restriction Fragment Length; D020641:Polymorphism, Single Nucleotide; D012737:Sex Factors; D044465:White People / Q000235:genetics
chemical_list: D020413:3' Untranslated Regions; D006637:Histamine N-Methyltransferase