title: Identification of an alternative 5'-untranslated exon and new polymorphisms of angiotensin-converting enzyme 2 gene: lack of association with SARS in the Vietnamese population.
abstract: We analyzed genetic variations of angiotensin-converting enzyme 2 (ACE2), considering that it might influence patients' susceptibility to severe acute respiratory syndrome-associated coronavirus (SARS-CoV) or development of SARS as a functional receptor. By cloning of the full-length cDNA of the ACE2 gene in the lung, where replication occurs on SARS-CoV, it was shown that there are different splicing sites. All exons including the new alternative exon, exon-intron boundaries, and the corresponding 5'-flanking region of the gene were investigated and 19 single nucleotide polymorphisms (SNPs) were found. Out of these, 13 SNPs including one non-synonymous substitution and three 3'-UTR polymorphisms were newly identified. A case control study involving 44 SARS cases, 16 anti-SARS-CoV antibody-positive contacts, 87 antibody-negative contacts, and 50 non-contacts in Vietnam, failed to obtain any evidence that the ACE2 gene polymorphisms are involved in the disease process in the population. Nevertheless, identification of new 5'-untranslated exon and new SNPs is considered helpful in investigating regulation of ACE2 gene expression in the future.
authors.affiliation: Department of Respiratory Diseases, Research Institute, International Medical Center of Japan, Tokyo, Japan.
authors.forename: Satoru
authors.initials: S
authors.lastname: Itoyama
authors.forename: Naoto
authors.initials: N
authors.lastname: Keicho
authors.forename: Minako
authors.initials: M
authors.lastname: Hijikata
authors.forename: Tran
authors.initials: T
authors.lastname: Quy
authors.forename: Nguyen Chi
authors.initials: NC
authors.lastname: Phi
authors.forename: Hoang Thuy
authors.initials: HT
authors.lastname: Long
authors.forename: Le Dang
authors.initials: LD
authors.lastname: Ha
authors.forename: Vo Van
authors.initials: VV
authors.lastname: Ban
authors.forename: Ikumi
authors.initials: I
authors.lastname: Matsushita
authors.forename: Hideki
authors.initials: H
authors.lastname: Yanai
authors.forename: Fumiko
authors.initials: F
authors.lastname: Kirikae
authors.forename: Teruo
authors.initials: T
authors.lastname: Kirikae
authors.forename: Tadatoshi
authors.initials: T
authors.lastname: Kuratsuji
authors.forename: Takehiko
authors.initials: T
authors.lastname: Sasazuki
mesh_terms: D024506:5' Flanking Region / Q000235:genetics*; D000293:Adolescent; D000328:Adult; D000368:Aged; D000483:Alleles; D017398:Alternative Splicing; D000085962:Angiotensin-Converting Enzyme 2; D002268:Carboxypeptidases / Q000235:genetics*; D016022:Case-Control Studies; D005091:Exons / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D007703:Peptidyl-Dipeptidase A; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D045169:Severe Acute Respiratory Syndrome / Q000201:enzymology / Q000235:genetics; D014744:Vietnam
chemical_list: D002268:Carboxypeptidases; D007703:Peptidyl-Dipeptidase A; C000705307:ACE2 protein, human; D000085962:Angiotensin-Converting Enzyme 2