Androgen receptor polyQ alleles and COVID-19 severity in men: a replication study

Background: Ample evidence indicates a sex-related difference in severity of COVID19, with less favorable outcomes observed in men. Genetic factors have been proposed as candidates to explain this difference. The polyglutamine (polyQ) polymorphism in the androgen receptor gene has been recently described as a genetic biomarker of COVID-19 severity. Objective: To test the association between the androgen receptor polyQ polymorphism and COVID-19 severity in a large cohort of COVID-19 male patients. Materials and methods: This study included 1136 male patients infected with SARSCoV-2 as confirmed by positive PCR. Patients were retrospectively and prospectively enrolled from March to November 2020. Patients were classified according to their severity into three categories: oligosymptomatic, hospitalized and severe patients requiring ventilatory support. The number of CAG repeats (polyQ polymorphism) at the androgen receptor was obtained by PCR and patients were classified as either short (<23 repeats) or long (≥23 repeats) allele carriers. The association between polyQ alleles (short or long) and COVID-19 severity was assessed by Chi-squared (Chi2) and logistic regression analysis. Results: The mean number of polyQ CAG repeats was 22 (±3). Patients were classified as oligosymptomatic (15.5%), hospitalized (63.2%), and severe patients (21.3%) requiring substantial respiratory support. PolyQ alleles distribution did not show significant differences between severity classes in our cohort (Chi2 test p > 0.05). Similar results were observed after adjusting by known risk factors such as age, comorbidities, and ethnicity (multivariate logistic regression analysis)Instituto de Salud Carlos III (ISCIII), Spanish Ministry of Science and Innovation (COVID-19 Research Call; COV20/00181) co-financed by European Development Regional Fund (FEDER, A way to achieve Europe); Estrella de Levante (E G-N); Colabora Mujer (E G-N); Instituto de Salud Carlos III (Centro de Investigación en Red de Enfermedades Raras, CIBERer); IIS-Fundación Jiménez Díaz-UAM Chair in Genomic Medicine; Instituto de Salud Carlos III (ISCIII), Spanish Ministry of Science and Innovation (Miguel Servet Contract Number: CP17/00006 and Juan Rodes Contract Number: JR17/00020) co-financied by European Regional Development Fund (FEDER); CEGEN-PRB3-ISCIII is funded by ISCIII and ERDF, Grant Number: PT17/001