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.
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.
Itoyama
Satoru
S
Department of Respiratory Diseases, Research Institute, International Medical Center of Japan, Tokyo, Japan.
Keicho
Naoto
N
Hijikata
Minako
M
Quy
Tran
T
Phi
Nguyen Chi
NC
Long
Hoang Thuy
HT
Ha
Le Dang
LD
Ban
Vo Van
VV
Matsushita
Ikumi
I
Yanai
Hideki
H
Kirikae
Fumiko
F
Kirikae
Teruo
T
Kuratsuji
Tadatoshi
T
Sasazuki
Takehiko
T
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
D002268:Carboxypeptidases; D007703:Peptidyl-Dipeptidase A; C000705307:ACE2 protein, human; D000085962:Angiotensin-Converting Enzyme 2