Unveiling sex-based impact of TYK2 rs2304256 polymorphism on interferon beta-1alpha responsiveness in COVID-19 patients

Abstract

Interferon beta-1a was one of the medications suggested by the World Health Organization in the COVID-19 therapy protocol in early 2020. IFNb-1a has previously been used to treat symptoms in multiple sclerosis patients. Previous studies have revealed that TYK2 and HLA genes play crucial roles in immune responses. The current study examined the relationship between TYK2 rs2304256, HLA-DQA1 rs9272105, and rs1448673 and the therapeutic response to IFNb-1a in COVID-19 patients from Kurdish ethnicity. A total of 124 patients with mild COVID-19 were included in this study. These patients received three injections of IFNb-1a every other day. The severity of COVID-19 symptoms and treatment response was determined using the World Health Organization (WHO) scoring method. Changes in WHO scores were assessed after five days, and patients with a difference of <0 were classified as responders (n = 74), whereas those with a difference of 0 or >0 were considered non-responders (n = 50). PCR techniques were used to genotype polymorphisms. The AG rs9272105 genotype reduced the treatment response (codominant model, OR = 0.37, P = 0.027; overdominant model, OR = 0.33, P = 0.011). Stratification by sex revealed that the AC and CC genotypes of rs2304256 reduced response to treatment in female and male patients, (p < 0.05), respectively. The rs2304256 and rs9272105 polymorphisms may play a role in the response to IFNb-1a treatment in COVID-19 patients.