The Association of Programmed Death 1 Gene Polymorphisms of PD1.3 G/A and PD1.5 C/T with Risk of COVID-19 in an Iranian Population: A Case-Control Study.

Programmed death 1 (PD-1) has a central role in maintaining T cell tolerance and terminating cellular responses after eliminating antigens. Variation in gene products caused by polymorphisms has been linked to several malignancies and autoimmune diseases. However, there is little known about the effects of its single-nucleotide polymorphisms (SNPs) on viral infections, particularly COVID-19. The primary aim of this study was to explore the function of genotypes, alleles, and haplotypes of two SNPs within the programmed cell death protein 1 () gene at PD1.3 G/A and PD1.5 C/T on susceptibility to COVID-19 in an Iranian population. The secondary objective was to evaluate the effects of these SNPs on the outcome of the disease. We got blood samples from COVID-19 patients ( = 195) and healthy subjects ( = 500) for genotypic determination of PD1.3 G/A (rs11568821) and PD1.5 C/T (rs2227981) SNPs, using the polymerase chain reaction-restriction fragment length polymorphism method, and constructed four haplotypes for SNPs. We used Pearson's chi-squared test, Fisher's exact test, and -test for this study and incorporated effect sizes of odds ratio (OR) and standardized mean difference. The frequency of CT genotype of PD1.5 was meaningfully higher in COVID-19 patients (49.2%) than in healthy subjects (37.4%) ( = 0.005). However, these significant differences were not observed in the frequencies of PD1.3 genotypes between the two groups ( > 0.05). Of all estimated haplotypes for , only AT was significantly and largely associated with COVID-19 susceptibility ( = 0.01, OR: 7.79 [95% confidence interval = 1.56-38.79]), however, this finding is inconclusive. In addition, the present study showed that the PD1.3 and PD1.5 SNPs were not associated with the outcome of the disease ( > 0.05). These results may propose that the PD1.5 CT genotype and AT haplotype of indecisively contribute to COVID-19 susceptibility in the Iranian population.