Frontiers in Microbiology (Nov 2022)

TMPRSS2 gene polymorphism common in East Asians confers decreased COVID-19 susceptibility

  • Takeshi Sekiya,
  • Yukino Ogura,
  • Hirayasu Kai,
  • Atsushi Kawaguchi,
  • Atsushi Kawaguchi,
  • Atsushi Kawaguchi,
  • Shino Okawa,
  • Mikako Hirohama,
  • Takahiro Kuroki,
  • Wataru Morii,
  • Akira Hara,
  • Yuji Hiramatsu,
  • Shigemi Hitomi,
  • Yasushi Kawakami,
  • Yoshihiro Arakawa,
  • Kazushi Maruo,
  • Shigeru Chiba,
  • Hiromichi Suzuki,
  • Hiroshi Kojima,
  • Hirokazu Tachikawa,
  • Kunihiro Yamagata

DOI
https://doi.org/10.3389/fmicb.2022.943877
Journal volume & issue
Vol. 13

Abstract

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COVID-19 has a wide range of clinical presentations, and the susceptibility to SARS-CoV-2 infection and the mortality rate also vary by region and ethnicity. Here, we found that rs12329760 in the TMPRSS2 gene, a missense variant common in East Asian populations, contributes to protection against SARS-CoV-2 infection. TMPRSS2 is a protease responsible for SARS-CoV-2 entry and syncytium formation. rs12329760 (c.478G>A, p. V160M) was associated with a reduced risk of moderate symptoms. The enzymatic activity of Met160-TMPRSS2 was lower than that of Val160-TMPRSS2, and thus the viral entry and the syncytium formation of SARS-CoV-2 were impaired. Collectively, these results indicate that the genetic variation in TMPRSS2, which is common in East Asians, is one of the molecular determinants of COVID-19 susceptibility.

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