Evidence map›Paper›PMID 39885568›Full record

ArticleHuman genomics2025

Genetic diversity of the immunoglobulin heavy chain locus in cohorts of patients affected with SARS-CoV-2.

Patrizia Malaspina, Carla Jodice, Bianca Maria Ciminelli, Michela Biancolella, Vito Luigi Colona, Andrea Latini, Francesca Leonardis, Paola Rogliani, Antonio Novelli, Giuseppe Novelli and 1 more

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Article in Human genomics, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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4 · The record

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5 · Who and what money

Authors and funding

11 authors.

Patrizia MalaspinaDepartment of Biology, Tor Vergata University of Rome, Via della Ricerca Scientifica 1, 00133, Rome, Italy. patrizia.malaspina@uniroma2.it.
Carla JodiceDepartment of Biology, Tor Vergata University of Rome, Via della Ricerca Scientifica 1, 00133, Rome, Italy.
Bianca Maria CiminelliDepartment of Biology, Tor Vergata University of Rome, Via della Ricerca Scientifica 1, 00133, Rome, Italy.
Michela BiancolellaDepartment of Biology, Tor Vergata University of Rome, Via della Ricerca Scientifica 1, 00133, Rome, Italy.
Vito Luigi ColonaResearch Unit of Neurorehabilitation, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy.
Andrea LatiniDepartment of Biomedicine and Prevention, Tor Vergata University of Rome, Rome, Italy.
Francesca LeonardisTor Vergata University Hospital, Rome, Italy.
Paola RoglianiTor Vergata University Hospital, Rome, Italy.
Antonio NovelliLaboratory of Medical Genetics, Translational Cytogenomics Research Unit, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy.
Giuseppe NovelliDepartment of Biomedicine and Prevention, Tor Vergata University of Rome, Rome, Italy.
Andrea NovellettoDepartment of Biology, Tor Vergata University of Rome, Via della Ricerca Scientifica 1, 00133, Rome, Italy.

Funding

HORIZON EUROPE European Research Council HORIZON-HLTH-2021-DISEASE-04 PROGRAM UNDER GRANT AGREEMENT N. 101057100 (UNDINE)
6 · The paper itself

Abstract

backgroundThe Immunoglobulin Heavy Chain (IGH) genomic region is responsible for the production of circulating antibodies and warrants careful investigation for its association with COVID-19 characteristics. Multiple allelic variants within and across different IGH gene segments form a limited set of haplotypes. Previous studies have shown associations between some of these haplotypes and clinical outcomes of COVID-19. We typed 445 individuals of European ancestry, stratified for gender, age, and clinical status for 4 SNPs, two of which result in amino acid substitutions in IGHA2 and IGHG4, respectively. We analyzed associations at the single-locus level and for 4-loci haplotypes, inferred by phasing, after stratifying the overall cohort by gender, age, and disease severity.

resultsOnly weak evidence of significant differences between subgroups was obtained at the level of a single SNP. However, when the haplotypic data were analyzed for the young and old subgroups separately, uneven partitioning was observed regarding the occurrence of severe cases and Resistors. We then examined the cross-tabulation of disease severity in males and females, based on the presence of each haplotype in the genotype. Two haplotypes were underrepresented in young severe cases compared to old severe ones. The same two haplotypes were overrepresented among young Resistors. These findings provide stronger support for, the weak associations observed at the single locus level.

conclusionsTwo haplotypes seem to act as protective factors specifically in young individuals, counteracting the general increase in vulnerability with age. This observation aligns with stronger genetic effects seen in young patients for other susceptibility genes. Our findings complement previous research identifying specific genetic variants that influence COVID-19 susceptibility and severity, emphasizing the complex interplay between host genetics and viral infection outcomes. Our results are consistent with a potential causative role of IGH regulatory regions (e.g. HS1.2), which are flanked by the SNP set here analyzed.

Indexed as

COVID-19Genetic VariationImmunoglobulin Heavy ChainsAdultAgedCohort StudiesFemaleGenetic Predisposition to DiseaseHaplotypesHumansMaleMiddle AgedPolymorphism, Single NucleotideSARS-CoV-2Severity of Illness IndexYoung AdultImmunoglobulin Heavy ChainsCOVID-19HaplotypesImmunoglobulin heavy chain gene segmentsSARS-CoV-2SNP

Identifiers

PMID39885568
PMCPMC11780896

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