Abstract
Purpose: The pandemic diffusion of Coronavirus Disease 2019 (COVID-19) has highlighted significant gender-related 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 (ERα) 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.
Keywords: Allelic polymorphisms; COVID-19 disease; IgH locus; Sex differences; hs1,2 enhancer.
【저자키워드】 COVID-19 disease, sex differences, Allelic polymorphisms, IgH locus, hs1,2 enhancer., 【초록키워드】 COVID-19, coronavirus disease, Coronavirus disease 2019, immune response, pandemic, Pneumonia, SARS-COV-2 infection, disease severity, hospital, Genetic, SNPs, Infection, haplotypes, Estrogen, Italy, clinical outcomes, COVID-19 disease, Clinical outcome, Region, Immunoglobulin, humans, Alpha, age, genetic variants, Genetic variant, receptor, women, distribution, COVID-19 patients, Clinical severity, nucleotide, linkage, severe disease, COVID-19 patient, heavy chain, DNA binding, locus, Blood samples, blood sample, protective factor, allele, genetic background, enhancer region, enhancer, diffusion, disequilibrium, MOST, Sex-related differences, men, Estrogen receptor alpha, genotyped SNPs, Occurrence, produced, collected, significantly, nine, exhibited, less, allelic, explain, hypothese, ERα, genotyped SNP, 【제목키워드】 Region, association, locus,