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

Takeshi Sekiya; Yukino Ogura; Hirayasu Kai; 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:10.3389/fmicb.2022.943877

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

Front Microbiol. 2022 Nov 30:13:943877. doi: 10.3389/fmicb.2022.943877. eCollection 2022.

Authors

Takeshi Sekiya¹, Yukino Ogura¹, Hirayasu Kai², Atsushi Kawaguchi^{1

3

4}, Shino Okawa⁵, Mikako Hirohama¹, Takahiro Kuroki⁶, Wataru Morii⁶, Akira Hara⁷, Yuji Hiramatsu⁸, Shigemi Hitomi⁹, Yasushi Kawakami¹⁰, Yoshihiro Arakawa¹¹, Kazushi Maruo¹², Shigeru Chiba¹³, Hiromichi Suzuki⁹, Hiroshi Kojima¹⁴, Hirokazu Tachikawa¹⁵, Kunihiro Yamagata²

Affiliations

¹ Department of Infection Biology, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan.
² Department of Nephrology, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan.
³ Transborder Medical Research Center, University of Tsukuba, Tsukuba, Japan.
⁴ Microbiology Research Center for Sustainability, University of Tsukuba, Tsukuba, Japan.
⁵ College of Biological Sciences, University of Tsukuba, Tsukuba, Japan.
⁶ Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tsukuba, Japan.
⁷ Department of Otorhinolaryngology, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan.
⁸ Department of Cardiovascular Surgery, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan.
⁹ Department of Infectious Diseases, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan.
¹⁰ Department of Laboratory Medicine, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan.
¹¹ Department of Medical Pharmacy, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan.
¹² Department of Biostatistics, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan.
¹³ Department of Hematology, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan.
¹⁴ Ibaraki Clinical Education and Training Center, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan.
¹⁵ Division of Clinical Medicine, Department of Disaster and Community Psychiatry, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan.

Abstract

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.

Keywords: COVID-19; SARS-CoV-2; SNP; tmprss2; virus entry.