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Exploring the Association of HLA Genetic Risk Burden on Thalamic and Hippocampal Atrophy in Multiple Sclerosis Patients

Multiple sclerosis (MS) is a complex disease of the central nervous system for which human leukocyte antigen (HLA) alleles are major contributors to susceptibility. Several investigations have focused on the relationship between HLA and clinical parameters, while few studies have evaluated its corre...

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Autores principales: Santoro, Silvia, Clarelli, Ferdinando, Preziosa, Paolo, Storelli, Loredana, Cannizzaro, Miryam, Mascia, Elisabetta, Esposito, Federica, Rocca, Maria Assunta, Filippi, Massimo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9690825/
https://www.ncbi.nlm.nih.gov/pubmed/36421810
http://dx.doi.org/10.3390/genes13112136
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author Santoro, Silvia
Clarelli, Ferdinando
Preziosa, Paolo
Storelli, Loredana
Cannizzaro, Miryam
Mascia, Elisabetta
Esposito, Federica
Rocca, Maria Assunta
Filippi, Massimo
author_facet Santoro, Silvia
Clarelli, Ferdinando
Preziosa, Paolo
Storelli, Loredana
Cannizzaro, Miryam
Mascia, Elisabetta
Esposito, Federica
Rocca, Maria Assunta
Filippi, Massimo
author_sort Santoro, Silvia
collection PubMed
description Multiple sclerosis (MS) is a complex disease of the central nervous system for which human leukocyte antigen (HLA) alleles are major contributors to susceptibility. Several investigations have focused on the relationship between HLA and clinical parameters, while few studies have evaluated its correlation with brain magnetic resonance imaging (MRI) measures. We investigated the association between the HLA genetic burden (HLAGB), originating from the most updated HLA alleles associated with MS, and neuroimaging endophenotypes, with a specific focus on brain atrophy metrics. A monocentric Italian cohort of 334 MS patients with imputed HLA alleles and cross-sectional volumetric measures of white matter (WM), gray matter (GM), hippocampus, thalamus and T2-hyperintense lesions was investigated. Linear regression models with covariate adjustment were fitted for each metric. We detected no effect of HLAGB on WM and GM volumes. Interestingly, we found a marginal correlation between higher HLAGB and lower hippocampal volume (β = −0.142, p = 0.063) and a nominal association between higher HLAGB and lower thalamic volume (β = −0.299, p = 0.047). No association was found with T2 lesion volumes. The putative impact of higher HLAGB on hippocampus and thalamus suggests, if replicated in independent cohorts, a possible cumulative contribution of HLA risk loci on brain volumetric traits linked to clinical deficits in MS.
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spelling pubmed-96908252022-11-25 Exploring the Association of HLA Genetic Risk Burden on Thalamic and Hippocampal Atrophy in Multiple Sclerosis Patients Santoro, Silvia Clarelli, Ferdinando Preziosa, Paolo Storelli, Loredana Cannizzaro, Miryam Mascia, Elisabetta Esposito, Federica Rocca, Maria Assunta Filippi, Massimo Genes (Basel) Article Multiple sclerosis (MS) is a complex disease of the central nervous system for which human leukocyte antigen (HLA) alleles are major contributors to susceptibility. Several investigations have focused on the relationship between HLA and clinical parameters, while few studies have evaluated its correlation with brain magnetic resonance imaging (MRI) measures. We investigated the association between the HLA genetic burden (HLAGB), originating from the most updated HLA alleles associated with MS, and neuroimaging endophenotypes, with a specific focus on brain atrophy metrics. A monocentric Italian cohort of 334 MS patients with imputed HLA alleles and cross-sectional volumetric measures of white matter (WM), gray matter (GM), hippocampus, thalamus and T2-hyperintense lesions was investigated. Linear regression models with covariate adjustment were fitted for each metric. We detected no effect of HLAGB on WM and GM volumes. Interestingly, we found a marginal correlation between higher HLAGB and lower hippocampal volume (β = −0.142, p = 0.063) and a nominal association between higher HLAGB and lower thalamic volume (β = −0.299, p = 0.047). No association was found with T2 lesion volumes. The putative impact of higher HLAGB on hippocampus and thalamus suggests, if replicated in independent cohorts, a possible cumulative contribution of HLA risk loci on brain volumetric traits linked to clinical deficits in MS. MDPI 2022-11-17 /pmc/articles/PMC9690825/ /pubmed/36421810 http://dx.doi.org/10.3390/genes13112136 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Santoro, Silvia
Clarelli, Ferdinando
Preziosa, Paolo
Storelli, Loredana
Cannizzaro, Miryam
Mascia, Elisabetta
Esposito, Federica
Rocca, Maria Assunta
Filippi, Massimo
Exploring the Association of HLA Genetic Risk Burden on Thalamic and Hippocampal Atrophy in Multiple Sclerosis Patients
title Exploring the Association of HLA Genetic Risk Burden on Thalamic and Hippocampal Atrophy in Multiple Sclerosis Patients
title_full Exploring the Association of HLA Genetic Risk Burden on Thalamic and Hippocampal Atrophy in Multiple Sclerosis Patients
title_fullStr Exploring the Association of HLA Genetic Risk Burden on Thalamic and Hippocampal Atrophy in Multiple Sclerosis Patients
title_full_unstemmed Exploring the Association of HLA Genetic Risk Burden on Thalamic and Hippocampal Atrophy in Multiple Sclerosis Patients
title_short Exploring the Association of HLA Genetic Risk Burden on Thalamic and Hippocampal Atrophy in Multiple Sclerosis Patients
title_sort exploring the association of hla genetic risk burden on thalamic and hippocampal atrophy in multiple sclerosis patients
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9690825/
https://www.ncbi.nlm.nih.gov/pubmed/36421810
http://dx.doi.org/10.3390/genes13112136
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