講演情報
[O33-2]コロナ重症化に関連するIL17遺伝子とコロナ発症に関わる唾液中のABO血液型抗原
○西田 奈央1, 杉山 真也1, 河合 洋介2, 土浦 貴代1, 石川 美由紀1, 徳永 勝士2, 溝上 雅史1 (1.国立国際医療研究センター ゲノム医科学プロジェクト, 2.国立国際医療研究センター ゲノム医科学プロジェクト（戸山）)
An international meta-analysis has been conducted to identify genetic factors associated with the onset and severity of COVID-19, but these factors have yet to be fully clarified. Here, we carried out genomic analysis based on a genome-wide association study (GWAS) in Japanese COVID-19 patients to determine whether genetic factors reported to be associated with the onset or severity of COVID-19 in the international meta-GWAS are replicated in the Japanese population, and whether new genetic factors exist. Although no significant genome-wide association was detected in the Japanese GWAS, an integrated analysis with the international meta-GWAS identified for the first time the involvement of the IL17A/IL17F gene in the severity of COVID-19. Among nine genes reported in the international meta-GWAS as genes involved in the onset of COVID-19, the association of FOXP4-AS1, ABO, and IFNAR2 genes was replicated in the Japanese population. Moreover, combined analysis of ABO and FUT2 genotypes revealed that the presence of oral AB antigens was significantly associated with the onset of COVID-19. FOXP4-AS1 and IFNAR2 were also significantly associated in the integrated analysis of the Japanese GWAS and international meta-GWAS when compared with severe COVID-19 cases and the general population. Individuals with the SNP risk allele found between IL17A and IL17F had significantly lower mRNA expression levels of IL17F, suggesting that activation of the innate immune response by IL17F may play an important role in the severity of SARS-CoV-2 infection.