Role of ACE1, ACE2, and CCR5-Δ32 Polymorphisms in the Transmission of SARS-CoV-2 to Intimate Contacts
Background. Despite the high transmissibility of SARS-CoV-2, some individuals remain uninfected despite prolonged exposure to a high viral load, suggesting the involvement of an innate resistance mechanism, possibly underpinned by the host’s genetic factors. The angiotensin-converting enzyme-1 (<...
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| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2025-05-01
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| Series: | Biology |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2079-7737/14/6/587 |
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| Summary: | Background. Despite the high transmissibility of SARS-CoV-2, some individuals remain uninfected despite prolonged exposure to a high viral load, suggesting the involvement of an innate resistance mechanism, possibly underpinned by the host’s genetic factors. The angiotensin-converting enzyme-1 (<i>ACE1</i>), <i>ACE2</i>, and C-C Chemokine Receptor 5 (<i>CCR5</i>) polymorphisms have been shown to influence susceptibility to the infection. In this study, the role of <i>ACE1</i>, <i>ACE2</i>, and <i>CCR5</i> gene polymorphisms in modulating susceptibility to SARS-CoV-2 infection within the context of intimate contact was evaluated. Methods. A cohort of heterosexual couples from Northern Sardinia, characterized by a homogenous genetic background, was recruited during the initial pandemic wave (March–June 2020). In each couple, one partner (index case) tested positive for SARS-CoV-2 by at least two consecutive independent molecular tests (real-time polymerase chain reaction: RT-PCR) on nasopharyngeal swabs. Bed-sharing partners of SARS-CoV-2 positive index cases, resistant and susceptible to the infection, were genotyped for <i>ACE1</i> 287 bp <i>Alu</i> repeat insertion/deletion (I/D) polymorphism, <i>ACE2</i> G8790A (<i>rs2285666</i>) variant, and a 32-base pair deletion (Δ32) of <i>CCR5</i>. Resistant and susceptible partners to the infection were compared for polymorphisms. Results. Out of 63 couples, 30 partners acquired SARS-CoV-2 infection, while 33 remained uninfected despite intimate exposure. Clinical history was minimal for current or past illnesses. SARS-CoV-2-infected index spouses and partners who acquired the infection developed a mild disease, not requiring hospitalization. The observed distribution of <i>ACE1</i> I/D and <i>ACE2</i> G8790A genotypes was consistent with previously reported frequencies in Sardinia and across European populations. None of the study participants carried the <i>CCR5-Δ32</i> variant. No statistically significant differences (<i>p</i> > 0.05) in the allelic or genotypic frequencies of these polymorphisms were observed between the infected and resistant partners. Conclusions. No differences in the distribution of <i>ACE1</i>, <i>ACE2</i>, and <i>CCR5</i> polymorphisms between the two groups were detected. These findings suggest that resistance is likely multifactorial, involving a complex interplay of genetic, immunological, and environmental factors. |
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| ISSN: | 2079-7737 |