Influence of HLA-A, -B, -DR Polymorphisms on the Severity of COVID-19: A Case-Control Study in the Iranian Population.

BACKGROUND: As an emerging pandemic disease, COVID-19 encompasses a spectrum of clinical diagnoses, from the common cold to severe respiratory syndrome. Considering the shreds of evidence demonstrating the relationship between human leukocyte antigen (HLA) allele diversity and infectious disease susceptibility, this study was conducted to determine the association of HLA alleles with COVID-19 severity in Iranian subjects. METHODS: In this case-control study, a total of 200 unrelated individuals (consisting of 100 people with severe COVID-19 and an average age of 55.54 as the case group, and 100 patients with mild COVID-19 with an average age of 48.97 as the control group) were recruited, and HLA typing (Locus A, B, and DR) was performed using the Olerup sequence-specific oligonucleotide (SSO) HLA-typing kit. RESULTS: Our results showed that HLA-A*11 and HLA-DRB1*14 alleles were more frequently observed in severe COVID-19 cases, while HLA-B*52 was more common in mild cases, which was in agreement with some previous studies. CONCLUSION: Our results confirmed the evidence for the association of HLA alleles with COVID-19 outcomes. We found that HLA-A*11 and HLA-DRB1*14 alleles may be susceptibility factors for severe COVID-19, while HLA-B*52 may be a protective factor. These findings provide new insight into the pathogenesis of COVID-19 and help patient management.

Validating MARK2 Gene Polymorphism as a Predictor of Response to Lithium Treatment in Bipolar Patients

Background: Lithium is a therapeutic option for the treatment of the acute phase of the bipolar disorder and long-term management of this disorder. However, it is estimated that 10 to 60% of patients do not properly response to this medication. Methods: To investigate the role of MARK2 gene in response to lithium, we genotyped the MARK2 rs10792421 polymorphism in Iranian bipolar patients using amplification Refractory Mutation System-PCR. Results: Results of this study showed a significant association of this polymorphism with response to lithium. The A allele was more frequent in the responder than the non-responder group and also in the semi- responder group compared to the non-responder group in the codominant model of analysis. AA and AG genotypes were more frequent in both the responder and semi-responder groups compared to the non-responder group in dominant model of analysis. Conclusion: Based on the findings of the current study, the rs10792421 variant of MARK2 gene could be considered as a potential biomarker for predicting the treatment outcome of bipolar disorder type 1 in Iranian population.

The Relationship between rs534654 Polymorphism in TMEM165 Gene and Increased Risk of Bipolar Disorder Type 1.

Bipolar disorder (BD) is a major health care concern worldwide. There are some reports showing an association between genes and their variants involved in circadian rhythm; clock and clock related genes function and development of BD in patients. Therefore, the aim of this study was to investigate the possible association of rs534654 variant on TMEM165 (transmembrane protein 165) gene with the risk of BD. Genotyping of the rs534654 was carried out using the tetra primers- amplification refractory mutation system-PCR (4P-ARMS-PCR) method in 203 patients with BD type 1 and their healthy and normal counterpart. The frequency of the G and A alleles of rs534654 polymorphism was 53% and 47%, respectively in patients. Genotype frequency in patients in comparison with control subjects was 5.4% vs 2.5% for the AA homozygous; 11.3% vs 80.8% for the GG homozygous; and 83.3% vs 16.7% for the heterozygous AG. Statistical analysis showed a significant difference in frequencies between the control and patient groups (P = 0.001). Based on this finding, it is possible to conclude that the impairment in the rs534654 single nucleotide polymorphism in TMEM165 gene is associated with the risk of BD development.

Investigation of the impact of an ADCY2 polymorphism as a predictive biomarker in bipolar disorder, suicide tendency and response to lithium carbonate therapy: the first report from Iran.

High rates of mortality due to both suicide and medical comorbidities in bipolar patients can be decreased through the administration of lithium, which affects the cerebral endothelium as well as neurons. To investigate the role of ADCY2 in risk of bipolar disorder, we genotyped the ADCY2 rs2290910 in bipolar patients and healthy controls using amplification refractory mutation system PCR. This polymorphism was associated with risk of bipolar disorder (odds ratio [OR]: 0.430; 95% CI: 0.296-0.624; p = 0.001). The C allele was more frequent in suicide ideation group compared other groups (OR: 2.7; 95% CI: 1.386-5.302; p = 0.004). The T allele was more frequent in suicide attempt group compared with suicide ideation group (OR: 0.238; 95% CI: 0.111-0.509; p = 0.001).