Gene . Functional associations between polymorphic regions of the human 3'IgH locus and COVID-19 disease

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Gene


. 2022 Jun 27;146698.
doi: 10.1016/j.gene.2022.146698. Online ahead of print.
Functional associations between polymorphic regions of the human 3'IgH locus and COVID-19 disease


Mattia Colucci ¹ , Domenico Frezza ² , Giovanni Gambassi ³ , Francesco De Vito ³ , Angela Iaquinta ³ , Maria Grazia Massaro ³ , Simona Di Giambenedetto ⁴ , Alberto Borghetti ⁴ , Francesca Lombardi ⁴ , Noemi Panzironi ¹ , Valentino Ruggieri ⁵ , Vincenzo Giambra ¹ , Rossella Cianci ⁶



Affiliations

• PMID: 35772651
• DOI: 10.1016/j.gene.2022.146698

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: COVID-19 disease; IgH locus; allelic polymorphisms; hs1,2; sex differences.