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medrxiv; 2023.
Preprint in English | medRxiv | ID: ppzbmed-10.1101.2023.08.19.23294314

ABSTRACT

Objectives: The clinical presentation of COVID-19 has shown high variability between individuals, which is partly due to genetic factors. The OAS1/2/3 cluster was found to be strongly associated with COVID-19 severity. We aimed to examine this locus for the occurrence of the critical variant, rs10774671, and its respective haplotype blocks within the Moroccan population. Methods: The frequency of SNPs at the cluster of OAS immunity genes was assessed from an in-house database in 157 unrelated individuals of Moroccan origin. The OAS1 exon 6 was sequenced by Sanger's method in 71 asymptomatic/mild and 74 moderate/severe individuals positive for SARS-CoV-2. Genotypic, allelic, and haplotype frequencies of three SNPs were compared between the two groups. Finally, males in our COVID-19 series were genotyped for the Berber-specific marker E-M81. Results: The prevalence of the OAS1 rs10774671-G allele in present-day Moroccans was 40.4%, close to that of Europeans. However, it was found equally on both the Neanderthal GGG haplotype and the African GAC haplotype with a frequency of 20% each. These two haplotypes, and hence the rs10774671-G allele, were significantly associated with the protection against severe COVID-19 (p = 0.034, p = 0.041, and p = 0.008 respectively). Surprisingly, among Berber men, the African haplotype was absent while the prevalence of the Neanderthal haplotype was close to that of Europeans. Conclusion: The protective rs10774671-G allele of OAS1 was found only in the Neanderthal haplotype in Berbers, the indigenous people of North Africa, suggesting that this region may have served as the stepping-stone for the passage of the hominids to the other continents.


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COVID-19
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