Purpose: The pandemic diffusion of Coronavirus Disease 2019 (COVID-19) has highlighted significant genderrelated differences in disease severity. Despite several hypotheses being proposed, how the genetic background of COVID-19 patients might impact clinical outcomes remains largely unknown. Methods: We collected blood samples from 192 COVID-19 patients (115 men, 77 women, mean age 67 +/- 19 years) admitted between March and June 2020 at two different hospital centers in Italy, and determined the allelic distribution of nine Single Nucleotide Polymorphisms (SNPs), located at the 3 ' Regulatory Region (3 ' RR)-1 in the immunoglobulin (Ig) heavy chain locus, including *1 and *2 alleles of polymorphic hs1.2 enhancer region. Results: In COVID-19 patients, the genotyped SNPs exhibited strong Linkage Disequilibrium and produced 7 specific haplotypes, associated to different degrees of disease severity, including the occurrence of pneumonia. Additionally, the allele *2, which comprises a DNA binding site for the Estrogen receptor alpha (ER alpha) in the polymorphic enhancer hs1.2 of 3 ' RR-1, was significantly enriched in women with a less severe disease. Conclusions: These findings document genetic variants associated to individual clinical severity of COVID-19 disease. Most specifically, a novel genetic protective factor was identified that might explain the sex-related differences in immune response to Sars-COV-2 infection in humans.
Colucci, M., Frezza, D., Gambassi, G., De Vito, F., Iaquinta, A., Massaro, M. G., Di Giambenedetto, S., Borghetti, A., Lombardi, F., Panzironi, N., Ruggieri, V., Giambra, V., Cianci, R., Functional associations between polymorphic regions of the human 3'IgH locus and COVID-19 disease, <<GENE>>, 2022; 838 (10.1016/j.gene.2022.146698): 146698-146698. [doi:10.1016/j.gene.2022.146698] [http://hdl.handle.net/10807/214187]
Functional associations between polymorphic regions of the human 3'IgH locus and COVID-19 disease
Gambassi, Giovanni;De Vito, Francesco;Massaro, Maria Grazia;Di Giambenedetto, Simona;Borghetti, Alberto;Lombardi, Francesca;Cianci, Rossella
2022
Abstract
Purpose: The pandemic diffusion of Coronavirus Disease 2019 (COVID-19) has highlighted significant genderrelated differences in disease severity. Despite several hypotheses being proposed, how the genetic background of COVID-19 patients might impact clinical outcomes remains largely unknown. Methods: We collected blood samples from 192 COVID-19 patients (115 men, 77 women, mean age 67 +/- 19 years) admitted between March and June 2020 at two different hospital centers in Italy, and determined the allelic distribution of nine Single Nucleotide Polymorphisms (SNPs), located at the 3 ' Regulatory Region (3 ' RR)-1 in the immunoglobulin (Ig) heavy chain locus, including *1 and *2 alleles of polymorphic hs1.2 enhancer region. Results: In COVID-19 patients, the genotyped SNPs exhibited strong Linkage Disequilibrium and produced 7 specific haplotypes, associated to different degrees of disease severity, including the occurrence of pneumonia. Additionally, the allele *2, which comprises a DNA binding site for the Estrogen receptor alpha (ER alpha) in the polymorphic enhancer hs1.2 of 3 ' RR-1, was significantly enriched in women with a less severe disease. Conclusions: These findings document genetic variants associated to individual clinical severity of COVID-19 disease. Most specifically, a novel genetic protective factor was identified that might explain the sex-related differences in immune response to Sars-COV-2 infection in humans.
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