American journal of respiratory and critical care medicine · 2022
A MUC5B Gene Polymorphism, rs35705950-T, Confers Protective Effects Against COVID-19 Hospitalization but Not Severe Disease or Mortality.
МетаанализСтатьяПоддержка правительства СШАПоддержка NIH: внешняя программаНазвание и аннотация: Перевод в очереди
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Verma Anurag, Minnier Jessica, Wan Emily S, Huffman Jennifer E, Gao Lina, Joseph Jacob, Ho Yuk-Lam, Wu Wen-Chih, Cho Kelly, Gorman Bryan R, Rajeevan Nallakkandi, Pyarajan Saiju, Garcon Helene, Meigs James B, Sun Yan V, Reaven Peter D, McGeary John E, Suzuki Ayako, Gelernter Joel, Lynch Julie A, Petersen Jeffrey M, Zekavat Seyedeh Maryam, Natarajan Pradeep, Dalal Sharvari, Jhala Darshana N, Arjomandi Mehrdad, Gatsby Elise, Lynch Kristine E, Bonomo Robert A, Freiberg Matthew, Pathak Gita A, Zhou Jin J, Donskey Curtis J, Madduri Ravi K, Wells Quinn S, Huang Rose D L, Polimanti Renato, Chang Kyong-Mi, Liao Katherine P, Tsao Philip S, Wilson Peter W F, Hung Adriana M, O'Donnell Christopher J, Gaziano John M, Hauger Richard L, Iyengar Sudha K, Luoh Shiuh-Wen, Million Veteran Program COVID-19 Science Initiative
Аннотация
Rationale: A common MUC5B gene polymorphism, rs35705950-T, is associated with idiopathic pulmonary fibrosis (IPF), but its role in severe acute respiratory syndrome coronavirus 2 infection and disease severity is unclear. Objectives: To assess whether rs35705950-T confers differential risk for clinical outcomes associated with coronavirus disease (COVID-19) infection among participants in the Million Veteran Program (MVP). Methods: The MUC5B rs35705950-T allele was directly genotyped among MVP participants; clinical events and comorbidities were extracted from the electronic health records. Associations between the incidence or severity of COVID-19 and rs35705950-T were analyzed within each ancestry group in the MVP followed by transancestry meta-analysis. Replication and joint meta-analysis were conducted using summary statistics from the COVID-19 Host Genetics Initiative (HGI). Sensitivity analyses with adjustment for additional covariates (body mass index, Charlson comorbidity index, smoking, asbestosis, rheumatoid arthritis with interstitial lung disease, and IPF) and associations with post-COVID-19 pneumonia were performed in MVP subjects. Measurements and Main Results: The rs35705950-T allele was associated with fewer COVID-19 hospitalizations in transancestry meta-analyses within the MVP (Ncases = 4,325; Ncontrols = 507,640; OR = 0.89 [0.82-0.97]; P = 6.86 × 10-3) and joint meta-analyses with the HGI (Ncases = 13,320; Ncontrols = 1,508,841; OR, 0.90 [0.86-0.95]; P = 8.99 × 10-5). The rs35705950-T allele was not associated with reduced COVID-19 positivity in transancestry meta-analysis within the MVP (Ncases = 19,168/Ncontrols = 492,854; OR, 0.98 [0.95-1.01]; P = 0.06) but was nominally significant (P < 0.05) in the joint meta-analysis with the HGI (Ncases = 44,820; Ncontrols = 1,775,827; OR, 0.97 [0.95-1.00]; P = 0.03). Associations were not observed with severe outcomes or mortality. Among individuals of European ancestry in the MVP, rs35705950-T was associated with fewer post-COVID-19 pneumonia events (OR, 0.82 [0.72-0.93]; P = 0.001). Conclusions: The MUC5B variant rs35705950-T may confer protection in COVID-19 hospitalizations.