Yousfi Fatima Zahra El, Haroun Abbas Ermilo, Nebhani Chaimae, Belayachi Jihane, Askander Omar, Fahime Elmostafa El, Fares Hakima, Ennibi Khalid, Abouqal Redouane, Razine Rachid, Bouhouche Ahmed
Laboratory of Human Genetics, Medical School and Pharmacy, University Mohammed V in Rabat, Rabat, Morocco.
Laboratory of Biostatistics, Clinical and Epidemiological Research, Department of Public Health, Medical School and Pharmacy, University Mohammed V in Rabat, Rabat, Morocco.
Arch Virol. 2024 Apr 25;169(5):109. doi: 10.1007/s00705-024-06038-y.
The clinical presentation of COVID-19 shows high variability among individuals, which is partly due to genetic factors. The OAS1/2/3 cluster has been found to be strongly associated with COVID-19 severity. We examined this locus in the Moroccan population for the occurrence of the critical variant rs10774671 and its respective haplotype blocks. The frequency of single-nucleotide polymorphisms (SNPs) in the cluster of OAS immunity genes in 157 unrelated individuals of Moroccan origin was determined using an in-house exome database. OAS1 exon 6 of 71 SARS-CoV-2-positive individuals with asymptomatic/mild disease and 74 with moderate/severe disease was sequenced by the Sanger method. The genotypic, allelic, and haplotype frequencies of three SNPs were compared between these two groups. Finally, males in our COVID-19 series were genotyped for the Berber-specific marker E-M81. The prevalence of the OAS1 rs10774671-G allele in present-day Moroccans was found to be 40.4%, which is similar to that found in Europeans. However, it was found equally in 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 protection against severe COVID-19 (p = 0.034, p = 0.041, and p = 0.008, respectively). Surprisingly, in men with the Berber-specific uniparental markers, the African haplotype was absent, while the prevalence of the Neanderthal haplotype was similar to that in Europeans. 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 a stepping-stone for the passage of hominids to other continents.
新冠病毒病（COVID-19）的临床表现存在高度个体差异，部分原因是遗传因素。已发现2'-5'-寡腺苷酸合成酶1/2/3（OAS1/2/3）基因簇与COVID-19的严重程度密切相关。我们在摩洛哥人群中研究了关键变异rs10774671及其各自的单倍型块的情况。利用内部外显子数据库确定了157名摩洛哥裔无关个体中OAS免疫基因簇中单核苷酸多态性（SNP）的频率。采用桑格测序法对71例无症状/轻症的新冠病毒2（SARS-CoV-2）阳性个体和74例中症/重症个体的OAS1第6外显子进行测序。比较了这两组中三个SNP的基因型、等位基因和单倍型频率。最后，对我们COVID-19系列中的男性进行了柏柏尔人特异性标记E-M81的基因分型。发现当今摩洛哥人中OAS1 rs10774671-G等位基因的频率为40.4%，与欧洲人相似。然而，在尼安德特人的GGG单倍型和非洲人的GAC单倍型中均有发现，频率均为20%。这两种单倍型，以及rs10774671-G等位基因，均与预防重症COVID-19显著相关（分别为p = 0.034、p = 0.041和p = 0.008）。令人惊讶的是，在具有柏柏尔人特异性单亲标记的男性中，非洲单倍型不存在，而尼安德特人单倍型的患病率与欧洲人相似。OAS1的保护性rs10774671-G等位基因仅在北非原住民柏柏尔人的尼安德特人单倍型中发现，这表明该地区可能是原始人类向其他大陆迁徙的跳板。
