Survey on the presence of rs179008 and rs17009 polymorphisms of TLR7 gene and its relationship with disease severity in patients with Covid-19
کد: G-08162
نویسندگان: Hadise Bagheri ©, Mehrdad Ravanshad
زمان بندی: زمان بندی نشده!
برچسب: ویروس شناسی پزشکی
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خلاصه مقاله:
Background and Aim
With the pandemic of the new corona virus, several studies were begun on this virus. In this study, two polymorphisms of TLR7 gene rs179008 and rs179009 that play an effective role in resistance and susceptibility to viral infections such as HCV, HBV, HIV, CMV were investigated. TLR7 is capable of detecting ss_RNA in innate immunity. It is mainly expressed in Bcells, monocytes and macrophages and pDCs. After binding to the TLR ligand, large amounts of pDCs (IFNa) induce a strong antiviral response in adjacent cells. Both IFNα induction and adaptive immunity are mediated by pDCs, which are considered important for TRL7 agonists to fight viruses, so to optimize and personalize treatment and selecting patients who benefit most from TLR7 agonist therapy It is important to note how genetic and environmental factors affect the response of pDCs to TLR7 agonists. TLR7 polymorphism (GLn11Leu), sex, and chronic virus all affect pDC IFN production. For example, Gln11Leu polymorphisms are directly associated with higher virus acquisition and loading, as well as faster disease progression in people with hepatitis C and HIV infection and basal cell carcinoma. TLR7 32A / T polymorphism in HIV-1 women was associated with disease progression compared to non-infected women.
Methods
test was performed on 160 CBC samples from people with Covid-19, which included 110 patients with mild disease and 50 patients with acute disease in the ICU ward. extraction was performed. Then, specific primers were designed using gene runner software. the main (outer) primer was designed to amplify the SNP locus, which was a 369-nucleotide product and as a control. Then, two specific primers were designed to check the presence of snp, the 3OH of the primers was placed on the SNP. in normal conditions and in the absence of snp, the primer was fully connected and reacted with the outer primer. We will have a product and if the snp primer is not fully connected, we will not have a product. so in normal conditions rs179009 primer will react with the outer forward primer and give a 144 nucleotide product and also rs179008 will react with the outer reverse primer and give a product of 87 nucleotides and finally a 369 nucleotide product as a control. This method does not determine whether the sample is heterozygous or homozygous, just shows the presence or absence of snp, base on studies this mutations is commonly homozygous.
Results
In this study, out of 160 samples, 110 were in mild condition and 50 were in ICU. In Mild group, 102patients (92.7%) had no mutation and 8 (7.3%) had rs179008 mutation. Similarly, in Severe group, 48 patients (96%) had no mutations and 2 patients (4%) had mutations. Also, rs179009 mutation was observed in only one of the samples. In total, the prevalence of rs179008 mutation was 6.25% in 160 patients and rs179009 was 0.65%. Therefore, a statistical relationship between severity and disease and this mutation was not observed in patients with Covid-19. Also, there is no significant relationship between rs179008 mutation and sex in this study (presence of mutation in women: 7.9, men: 4.8%) Similarly, a study by Sonja I. Buschow et al. Showed that the rs179008 allele is predominantly absent in Asians and is more common in Caucasians. According to the articles, the prevalence of rs179009 in Asia and East Asia is reported to be 5-15% and rs179008 is about 0-5%. Therefore, these two polymorphisms are not influential factors in the severity of couvid-19 pathogenicity due to the effect on the function of innate immune cells, especially pDCs, in interferon production
Conclusion
Considering that these two polymorphisms played an important role in the resistance and susceptibility of individuals to viral infections, especially HCV, this study was performed which showed that due to the role of these two polymorphisms in innate immunity, especially in pDCs in production Interferon is not a logical relationship between the prevalence of these two polymorphisms and the severity and susceptibility of individuals to this disease. Also, a logical relationship between gender and disease severity was not observed in this study. But a study by Seillet et al et al. Concluded that pDC function is also influenced by gender: Male pDCs produce less IFNα by TLR7 than female pDCs. This difference is due to the difference in the expression of X chromosome genes in the TLR7 stream, along with hormonal effects.Due to the presence of some patients with underlying diseases such as hypertension, hyperlipidemia, asthma, diabetes due to the small number of cases in our study, the statistical relationship is only between people with diabetes and Asthma was observed. For better results, more studies are needed in the higher statistical community.
Keywords
covid-19; corona virus; TLR7; polymorphism; rs179008; rs 179009
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