Variant Allele of <i>ALDH2</i>, rs671, Associates with Attenuated Post-Vaccination Response in Anti-SARS-CoV-2 Spike Protein IgG: A Prospective Study in the Japanese General Population
Akiko Matsumoto,
Megumi Hara,
Mohammad Said Ashenagar,
Mikiko Tokiya,
Takeshi Sawada,
Chiharu Iwasaka,
Takuma Furukawa,
Kyoko Kitagawa,
Yasunobu Miyake,
Yoshio Hirota
Affiliations
Akiko Matsumoto
Department of Social and Environmental Medicine, School of Medicine, Saga University, 5-1-1 Nabeshima, Saga 849-8501, Japan
Megumi Hara
Department of Preventive Medicine, Faculty of Medicine, Saga University, 5-1-1 Nabeshima, Saga 849-8501, Japan
Mohammad Said Ashenagar
Department of Social and Environmental Medicine, School of Medicine, Saga University, 5-1-1 Nabeshima, Saga 849-8501, Japan
Mikiko Tokiya
Department of Social and Environmental Medicine, School of Medicine, Saga University, 5-1-1 Nabeshima, Saga 849-8501, Japan
Takeshi Sawada
Division of Histology and Neuroanatomy, Department of Anatomy and Physiology, Faculty of Medicine, Saga University, 5-1-1 Nabeshima, Saga 849-8501, Japan
Chiharu Iwasaka
Department of Preventive Medicine, Faculty of Medicine, Saga University, 5-1-1 Nabeshima, Saga 849-8501, Japan
Takuma Furukawa
Department of Preventive Medicine, Faculty of Medicine, Saga University, 5-1-1 Nabeshima, Saga 849-8501, Japan
Kyoko Kitagawa
Department of Environmental Health, University of Occupational and Environmental Health, 1-1 Iseigaoka, Yahatanishi-ku, Kitakyushu 807-8555, Japan
Yasunobu Miyake
Division of Molecular and Cellular Immunoscience, Department of Biomolecular Sciences, Faculty of Medicine, Saga University, Saga 840-8501, Japan
Yoshio Hirota
SOUSEIKAI Medical Group, Clinical Epidemiology Research Center, Medical Co., LTA, 3-6-1 Kashii-Teriha, Higashi-Ku, Fukuoka 813-0017, Japan
Uncovering the predictors of vaccine immunogenicity is essential for infection control. We have reported that the most prevalent polymorphism of the aldehyde dehydrogenase 2 gene (ALDH2), rs671, may be associated with an attenuated immune system. To test the inverse relationship between rs671 and antibody production after COVID-19 vaccination, the levels of anti-SARS-CoV-2 Spike protein S1 subunit (S1) IgG were repeatedly measured for four months before and after vaccination with BNT162b2 or mRNA-1273, in 88 Japanese workers and students (including 45 females, aged 21–56 years, with an rs671 variant allele frequency of 0.3). The mixed model including fixed effects of the vaccine type, weeks post vaccination (categorical variable), sex, age, height, smoking status, ethanol intake, exercise habit, perceived stress, steroid use, allergic diseases, and dyslipidemia, indicated an inverse association between log-transformed anti-S1 IgG levels and the number of rs671 variant alleles (partial regression coefficient = −0.15, p = 0.002). Our study indicated for the first time that the variant allele of ALDH2, rs671, is associated with the attenuated immunogenicity of COVID-19 mRNA vaccines. Our finding may provide a basis for personalized disease prevention based on a genetic polymorphism that is prevalent among East Asians.
