Department of Genetics and Genomics, Instituto de Investigación Sanitaria-Fundación Jiménez Díaz University Hospital, Universidad Autónoma de Madrid (IIS-FJD, UAM), Madrid, Spain.
Center for Biomedical Network Research on Rare Diseases (CIBERER), Instituto de Salud Carlos III, Madrid, Spain.
Andrology. 2023 Jan;11(1):24-31. doi: 10.1111/andr.13339. Epub 2022 Nov 28.
Ample evidence indicates a sex-related difference in severity of COVID-19, 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.
To test the association between the androgen receptor polyQ polymorphism and COVID-19 severity in a large cohort of COVID-19 male patients.
This study included 1136 male patients infected with SARS-CoV-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 (Chi ) and logistic regression analysis.
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).
Androgen sensitivity may be a critical factor in COVID-19 disease severity. However, we did not find an association between the polyQ polymorphism and the COVID-19 severity. Additional studies are needed to clarify the mechanism underlying the association between androgens and COVID-19 outcome.
The results obtained in our study do not support the role of this polymorphism as biomarker of COVID-19 severity.
大量证据表明，COVID-19 的严重程度存在性别差异，男性的预后较差。遗传因素被认为是造成这种差异的候选因素。雄激素受体基因中的多聚谷氨酰胺（polyQ）多态性最近被描述为 COVID-19 严重程度的遗传生物标志物。
在一组大量 COVID-19 男性患者中，检测雄激素受体 polyQ 多态性与 COVID-19 严重程度之间的关系。
本研究纳入了 1136 名经 PCR 检测证实感染 SARS-CoV-2 的男性患者。患者于 2020 年 3 月至 11 月间回顾性和前瞻性入组。根据病情严重程度将患者分为三组：症状轻微、住院和需要呼吸机支持的重症患者。雄激素受体的 CAG 重复数（polyQ 多态性）通过 PCR 获得，患者分为短（<23 个重复）或长（≥23 个重复）等位基因携带者。通过卡方（Chi ）和逻辑回归分析评估 polyQ 等位基因（短或长）与 COVID-19 严重程度之间的关系。
polyQ CAG 重复的平均数量为 22（±3）。患者被分为症状轻微（15.5%）、住院（63.2%）和需要大量呼吸支持的重症患者（21.3%）。在我们的队列中，polyQ 等位基因的分布在严重程度分类之间没有显著差异（卡方检验 p>0.05）。在调整了年龄、合并症和种族等已知危险因素后，也得到了类似的结果（多变量逻辑回归分析）。
雄激素敏感性可能是 COVID-19 疾病严重程度的关键因素。然而，我们没有发现 polyQ 多态性与 COVID-19 严重程度之间的关联。需要进一步的研究来阐明雄激素与 COVID-19 结局之间关联的机制。
我们的研究结果不支持该多态性作为 COVID-19 严重程度生物标志物的作用。
