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

Itoyama, Satoru; Keicho, Naoto; Hijikata, Minako; Quy, Tran; Phi, Nguyen Chi; Long, Hoang Thuy; Ha, Le Dang; Ban, Vo Van; Matsushita, Ikumi; Yanai, Hideki; Kirikae, Fumiko; Kirikae, Teruo; Kuratsuji, Tadatoshi; Sasazuki, Takehiko

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. © 2005 Wiley‐Liss, Inc.