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. 2022 Aug 15;23(16):9171.
doi: 10.3390/ijms23169171.

Allelic Variations in the Human Genes TMPRSS2 and CCR5, and the Resistance to Viral Infection by SARS-CoV-2

Girolamo Aurelio Vitello  1 , Concetta Federico  2 , Francesca Bruno  2 , Mirella Vinci  1 , Antonino Musumeci  1 , Alda Ragalmuto  1 , Valentina Sturiale  2 , Desiree Brancato  2 , Francesco Calì  1 , Salvatore Saccone  2
Affiliations

Allelic Variations in the Human Genes TMPRSS2 and CCR5, and the Resistance to Viral Infection by SARS-CoV-2

Girolamo Aurelio Vitello et al. Int J Mol Sci. .

Abstract

During the first wave of COVID-19 infection in Italy, the number of cases and the mortality rates were among the highest compared to the rest of Europe and the world. Several studies demonstrated a severe clinical course of COVID-19 associated with old age, comorbidities, and male gender. However, there are cases of virus infection resistance in subjects living in close contact with infected subjects. Thus, to explain the predisposition to virus infection and to COVID-19 disease progression, we must consider, in addition to the genetic variability of the virus and other environmental or comorbidity conditions, the allelic variants of specific human genes, directly or indirectly related to the life cycle of the virus. Here, we analyzed three human genetic polymorphisms belonging to the TMPRSS2 and CCR5 genes in a sample population from Sicily (Italy) to investigate possible correlations with the resistance to viral infection and/or to COVID-19 disease progression as recently described in other human populations. Our results did not show any correlations of the rs35074065, rs12329760, and rs333 polymorphisms with SARS-CoV-2 infection or with COVID-19 disease severity. Further studies on other human genetic polymorphisms should be performed to identify the major human determinants of SARS-CoV-2 viral resistance.

Keywords: CCR5 gene; COVID-19; SARS-CoV-2 first wave infection; TMPRSS2 gene; rs12329760; rs333; rs35074065.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Frequency of the three genotypes obtained by the C and delC alleles of the rs35074065 SNP polymorphism (TMPRSS2 gene) in the analyzed groups. (Left) Genotype frequency in the total subjects (Chi-square Test for 3 × 2: Chi = 0.019 p = 0.991 df = 2; Sample size = 102; power = 0.132740). (Middle) Genotype frequency in the subjects belonging to the analyzed families with cohabiting members (Chi-square Test for 3 × 2: Chi = 0.1119 p = 0.9456 df = 2). (Right) Genotype frequency in the subjects belonging to the intellectual disability patients cohabiting in the Oasi M. Santissima IRCCS (Troina, Italy) (Chi-square Test for 3 × 2: Chi = 2.65 p = 0.265 df = 2). Each group was subdivided into infected (COVID-19 Pos.) and non-infected (COVID-19 Neg.) groups. No statistically significant correlation was obtained between SARS-CoV-2 infection and the rs35074065 SNP polymorphism.
Figure 2
Figure 2
Frequency of the three genotypes obtained by the C and T alleles of the rs12329760 SNP polymorphism (TMPRSS2 gene) in the analyzed groups. (Left) Genotype frequency in the total subjects (Chi-square Test for 3 × 2: Chi = 1.282 p = 0.527 df = 2; Sample size = 102; power = 0.0922357). (Middle) Genotype frequency in the subjects belonging to the analyzed families with cohabiting members (Chi-square Test for 3 × 2: Chi = 3.207 p = 0.2011 df = 2). (Right) Genotype frequency in the subjects belonging to the intellectual disability patients cohabiting in the Oasi M. Santissima IRCCS (Troina, Italy). Each group was subdivided into infected (COVID-19 Pos.) and non-infected (COVID-19 Neg.) groups. (Chi-square Test for 3 × 2: Chi = 2.0812 p = 0.353 df = 2). No statistically significant correlation was obtained between SARS-CoV-2 infection and the rs12329760 SNP polymorphism.
Figure 3
Figure 3
Frequency of the three genotypes obtained by the wild-type (wt) and ∆32 alleles of the rs333 SNP polymorphism (CCR5 gene) in the analyzed groups. (Left) Genotype frequency in the total subjects (Chi-square Test for 2 × 2: Chi = 0.00004 p = 0.995 df = 1; Sample size = 102; power = 0.15933). (Middle) Genotype frequency in the subjects belonging to the analyzed families with cohabiting members (Chi-square Test for 2 × 2: Chi = 2.8948 p = 0.0888; df = 1). (Right) Genotype frequency in the subjects belonging to the intellectual disability patients cohabiting in the Oasi M. Santissima IRCCS (Troina, Italy). Each group was subdivided into infected (COVID-19 Pos.) and non-infected (COVID-19 Neg.) groups. Chi-square Test for 2 × 2: Chi= 0.1331 p = 0.7153; df = 1). No statistically significant correlation was obtained between SARS-CoV-2 infection and the rs333 SNP polymorphism.
Figure 4
Figure 4
Genotype distribution of the rs35074065, rs12329760, and rs333 polymorphisms in the intellectual disability patients cohabiting in the Oasi M. Santissima IRCCS (Troina, Italy) sub-divided by severity of COVID-19 disease. rs35074065: Chi-square = 5.482, p = 0.483, df = 6; rs12329760: Chi-square = 3.077, p = 0.799, df = 6; and rs333: Chi-square = 3.792, p = 0.284, df = 3. No statistically significant correlation was obtained between disease severity and the three polymorphisms analyzed.
Figure 5
Figure 5
Visualization of the genotypes for the rs12329760, rs35074065, and rs333 polymorphisms. (A) Sanger sequencing electropherograms for the rs12329760 polymorphism of the TMPRSS2 gene. (B) Sanger sequencing electropherograms for the rs35074065 polymorphism of the TMPRSS2 gene. (C) Gene Mapper visualization of the rs333 polymorphism of the CCR5 gene. All the genotypes are indicated.
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